Abstract
Current research into the role of engineered nanomolecules in drug delivery systems (DDSs) for medical purposes has developed numerous fascinating nanocarriers. This paper reviews the various conventionally used and current used carriage system to deliver drugs. Due to numerous drawbacks of conventional DDSs, nanocarriers have gained immense interest. Nanocarriers like polymeric nanopar- ticles, mesoporous nanobots(molecules), nanomaterials, carbon nanotubes, dendrimers, liposomes, metallicnanomolecules, nanomedicine, and engineered nanomaterials are used as carriage systems for targeted delivery at specific sites of affected areas in the body. Nanomedicine has rapidly grown to treat certain diseases like brain cancer, lung cancer, breast cancer, cardiovascular diseases, and many others. These nanomedicines can improve drug bioavailability and drug absorption time, reduce release time, elimi- nate drug aggregation, and enhance drug solubility in the blood. Nanomedicine has introduced a new era for drug carriage by refining the therapeutic directories of the energetic pharmaceutical elements engineered within nanomolecules. In this context, the vital information on engineered nanomolecules was reviewed and conferred towards the role in drug carriage systems to treat many ailments. All these nanocarriers were tested in vitro and in vivo. In the coming years, nanomedicines can improve human health more effectively by adding more advanced techniques into the drug delivery system. In coming years, nanotechnology is likely to have a significant impact in different fields like medicine and electronics. Nanorobotics is emerging as a demanding field dealing with miniscule things at molecular level. Nano robots perform a specific task with precision at nanoscale dimensions. Nano robots are especially used for studies on Alzheimer disease and cancer treatments. These can be seen as the first Nano medicines, with potential application in medicine. Present day treatment includes surgeries which are considered outdated when compared to today’s technology.
Keywords
Drug Delivery; Nanomedicine; Therapeutics; Nanomolecules; Personalized Medicine; Nanorobots; Design; Types; Applications
Introduction
Drug delivery systems (DDSs) have been used in past eras to treat numerous ailments. All medicines rely on pharmacologic active metabolites (drugs) to treat diseases [1]. Some ofthe drugs are designed as the inactive precursor, but they become active when transformed in the body [2]. Their effectiveness depends on the route of administration. In conventional drug delivery systems (CDDSs), drugs were delivered usually via oral, nasal, inhaled, mucosal, and shot methods [3]. The conventionally delivered drugs were absorbed less, distributed randomly, damaged unaffected areas, were excreted early, and took a prolonged time to cure the disease [4]. They were less effective due to many hurdles like their enzymatic degradation or disparity in pH, many mucosal barriers, and off-the-mark effects, and their immediate release enhanced toxicity in blood [5]. Due to all such reasons, the controlled-release drug delivery system was developed. Such evolution in the DDS enhances drug effectiveness in many ways [6]. DDSs have been engineered in recent years to control drug release [7]. Such engineered DDSs used various novel strategies for controlled drug release into the diseased areas. These strategies were erodible material, degradable material, matrix, hydrogel, osmotic pump, and reservoir [8]. they all provided a medium for the medicines to deliver at the desired sites like tissues, cells,or organs. In these approaches, drugs are often available for many diseases [9]. Such strategies were unsuccessful due to lower distribution, less solubility, higher drug aggregation, less target selection, and poor effects for disease treatment [10]. Moreover, drug development is the most expensive, intricate, and time-consuming process [5]. The innovative drug findings involved the identification of new chemical entities (NCEs), [11] having the vital distinguishing characteristics of drug capacity and pharmaceutical chemistry. This methodology, however, was confirmed to be less effective in terms of the overall attainment percentage [12], as 40% of drug development was botched due to its changeable responses and unpredicted noxiousness in humans [13]. From past decades until now, drug development and its delivery are shiftingfrom the micro to the nano level to prolong life expectancy by revolutionizing drug deliverysystems (Figure 1) [14].
Figure 1. Illustration of how traditional medications were administered without the use of nanocarri- ers and harm was done to healthy organs or cells. In contrast, modern procedures use nanomedicines to transport medications to specific parts of the body.
In 1959, Feynman was the first physicist to introduce the notion of nanotechnology in the lecture entitled “There’s Plenty of oom at the Bottom”. This concept initiated remarkable developments in the arena of nanotechnology [15]. Nanotechnology is the study of extremely tiny things and is basically the hub of all science disciplines including physics, chemistry, biology, engineering, information technology, electronics, and material science [16]. The structures measured with nanotechnology range from 1–100 nm at the nanoscale level [17]. Nanoparticles have different material characteristics because of submicroscopic size and also provide practical implementations in a wide range of fields including engineering, drug delivery, nanomedicine, environmental indemnification, and catalysis, as well as target diseases such as melanoma and cardiovascular diseases (CVD), skin diseases, liver diseases, and many others [18]. Therefore, medicines linked with nanotechnology can enhance efficiency of medicines and their bioavailability [19]. The relation of nanomolecules to biomedicine was demon- strated in late the 1970s, and over 10,000 publications have referred to this association with the term “nanomedicine”. Almost thirty papers on this term were accessible by 2005 [20]. After 10 to 12 years, Web of Science published more than 1000 nanomedicine articles in 2015 and most of the articles relating nanomolecules (NPs) for biomedical usage [21]. Nanocarriers such as dendrimers, liposomes, peptide-based nanomolecules, carbon nano tubes, quantum dots, polymer-based nanomolecules, inorganic vectors, lipid-based nanopar- ticles, hybrid NPs, and metal nanomolecules are the advanced forms of NPs [22]. Nanoparti- cles are nowadays a growing arena for drug delivery, microfluidics, biosensors, microarrays, and tissue micro- engineering for the specialized treatment of diseases [23–25]. Nanoparticles are less effective and can treat cancer by selectively killing all cancerous cells [26]. In 2015, the Food and Drug Administration (FDA) approved the clinical trials of onivyde nanomedicine in the treatment of cancer [27]. The characteristic properties of nanocarriers are physicochemical properties, supporting the drugs by improving solubility, degradation, clearance, targeting, theranostics, and combination therapy [28]. Studies on nanomedicine based on protein used for drug delivery in which various protein subunits combine to deliver medicine on site to a specific tumor have been reported [29]. Many altered kinds and forms of nanocarriers arranged to carry medicine are protein-based podiums, counting several protein coops, nanomolecules, hydrogels, films, microspheres, tiny rods, and minipellets [30]. All proteins, including ferritin–protein coop, the small heat shock protein (sHsp) cage, plant-derived viral capsids, albumin, soy and whey protein, collagen, and gelatin-implemented proteins are characterized for drug carriage [31]. The nanomedicines are escorted in a new-fangled epoch, meant for drug carriage byrefining the therapeutic directories of the energetic pharmacological elements engineered inside nanomolecules [32]. In this epoch, nanomedicine-based targeted-design structurescan deliver multipurpose freight with favorable pharmacokinetics and capitalized so as to enhance drug specificity, usefulness, and safety, as shown in (Figure 2) [33]. The failureof chemotherapeutic approaches has increased the recurrence chances of disease, whichenhances the complexity of lethal diseases [34].
Figure 2. Aids of using nanomedicine platform for delivering drugs to the tumor complex.
HISTORY
Petros and his colleague reported a study about mid-19th century work on nan- otechnology. As they reported, polymers and drugs were conjugated in 1955 [35], the first controlled-release polymer device appeared in 1964, the liposome was discovered by Bangham in 1965, albumin- based NPs were reported in 1972, liposome-based drugs were formulated in 1973, the first micelle was formulated and approved in 1983, the FDA approved the first controlled formulation in 1989, and first polyethylene glycol (PEG) conjugated with protein entered the market in 1990 [36]. Further studies have produced incredibly encouraging results for treating a variety of disorders.
- Recent Approaches Used in Drug Carriage System for Treatment of Various Diseases
- Brain Drug Delivery System and Its Types
Under the most pathological circumstances of diseases such as strokes, seizures, mul- tiple sclerosis, AIDS, diabetes, glioma, Alzheimer’s disease, and Parkinson’s disease, the blood–brain barrier (BBB) is disrupted [103]. An important reason for the breakdownof the blood–brain barrier is the remodeling of the protein complex in intra-endothelial junctions under the pathological conditions [104]. Normally, the blood–brain barrier actsto maintain blood–brain homeostasis by preventing entry of macromolecules and micro- molecules from the blood [105]. If a drug crosses the BBB, it restricts accumulation of the drug in the intracerebral region of brain, and bioavailability is reduced, due to which brain diseases cannot be treated [106]. Therefore, the optimal drug delivery system (DDS) is a cell membrane DDS, virus-based DDS, or exosome- based DDS designed for BBB pene- trability, lesion-targeting ability, and standard safety [107]. For the cure of brain diseases, the nanocarrier-assisted intranasal drug carriage system is widely used [108]. Now, at the advanced level, drugs poorly distributed to the brain can be loaded into a nanocarrier-based system, which would interact well with the endothelial micro vessel cells at the BBB and nasal mucosa to increase drug absorption time and the olfactory nerve fibers to stimulate straight nose-to- brain delivery [109], thus greater drug absorption in brain parenchyma through the secondary nose- to-blood-to-brain pathway [110]. The current strategies used are viral vectors, nanomolecules, exosomes, brain permeability enhancers, delivery through active transporters in the BBB, alteration of administration route, nanomolecules for the brain, and imaging/diagnostics under diseased conditions [111].
a. Role of Nanocarriers in Alzheimer’s Disease
Alzheimer’s disease is one of the fastest growing neurodegenerative diseases in the elderly population. Clinically, it is categorized by abstraction, damage to verbal access, and diminishing in spatial skills and reasoning [112]. Furthermore, engrossment of amyloid ? (A?) aggregation and anxiety in the brain have significant parts [113]. The treatment of different diseases with nanotechnology-based drug delivery uses nanotechnology-based approaches [114]. In Alzheimer’s diseases, polymeric nanomolecules, liposomes, solid lipid nanomolecules, nano-emulsions, micro-emulsions, and liquid-crystals are used for treatment.
Polymeric Nanoparticles
- The drug Tacrine was loaded on polymeric nanomolecules and administered throughan intravenous route. It enhanced the concentration of tacrine inside the brain and also reduced the whole-dose quantity [115].
- Rivastigmine drug was loaded on polymeric nanomolecules and administered through an intravenous route. It enhanced learning and memory capacities [116].
Solid Lipid Nanoparticles (SLNPs)
SLNPs enhanced drug retention in the brain area, raising absorption across the BBB [117]. Some of the drug’s effects are listed below.
- Piperine drug is loaded on solid lipid nanomolecules through an intraperitoneal route inside the brain to decrease plaques and masses and to increase AChE enzyme activity [118].
- Huperzine A improved cognitive functions. No main irritation was detected in rat skin
when the drug was loaded on SLNPs in an in vitro study [119].
In recent reports, the coating of SLNPs with polysorbate enhances drug bioavailabil- ity [120,121]. Some of the coated NPs are listed below.
- The drug clozapine was loaded on a Dynasan 116 [Tripalmitin] lipid matrix coated with surfactant Poloxamer 188, Epikuron 200 to unload the drug safely into the brain microenvironment [122,123].
- Recent Approaches Used in Drug Carriage System for Treatment of Various Diseases
- Brain Drug Delivery System and Its Types
Under the most pathological circumstances of diseases such as strokes, seizures, mul- tiple sclerosis, AIDS, diabetes, glioma, Alzheimer’s disease, and Parkinson’s disease, the blood–brain barrier (BBB) is disrupted [103]. An important reason for the breakdownof the blood–brain barrier is the remodeling of the protein complex in intra-endothelial junctions under the pathological conditions [104]. Normally, the blood–brain barrier actsto maintain blood–brain homeostasis by preventing entry of macromolecules and micro- molecules from the blood [105]. If a drug crosses the BBB, it restricts accumulation of the drug in the intracerebral region of brain, and bioavailability is reduced, due to which brain diseases cannot be treated [106]. Therefore, the optimal drug delivery system (DDS) is a cell membrane DDS, virus-based DDS, or exosome- based DDS designed for BBB pene- trability, lesion-targeting ability, and standard safety [107]. For the cure of brain diseases, the nanocarrier-assisted intranasal drug carriage system is widely used [108]. Now, at the advanced level, drugs poorly distributed to the brain can be loaded into a nanocarrier-based system, which would interact well with the endothelial micro vessel cells at the BBB and nasal mucosa to increase drug absorption time and the olfactory nerve fibers to stimulate straight nose-to- brain delivery [109], thus greater drug absorption in brain parenchyma through the secondary nose- to-blood-to-brain pathway [110]. The current strategies used are viral vectors, nanomolecules, exosomes, brain permeability enhancers, delivery through active transporters in the BBB, alteration of administration route, nanomolecules for the brain, and imaging/diagnostics under diseased conditions [111].
a. Role of Nanocarriers in Alzheimer’s Disease
Alzheimer’s disease is one of the fastest growing neurodegenerative diseases in the elderly population. Clinically, it is categorized by abstraction, damage to verbal access, and diminishing in spatial skills and reasoning [112]. Furthermore, engrossment of amyloid ? (A?) aggregation and anxiety in the brain have significant parts [113]. The treatment of different diseases with nanotechnology-based drug delivery uses nanotechnology-based approaches [114]. In Alzheimer’s diseases, polymeric nanomolecules, liposomes, solid lipid nanomolecules, nano-emulsions, micro-emulsions, and liquid-crystals are used for treatment.
Polymeric Nanoparticles
- The drug Tacrine was loaded on polymeric nanomolecules and administered throughan intravenous route. It enhanced the concentration of tacrine inside the brain and also reduced the whole-dose quantity [115].
- Rivastigmine drug was loaded on polymeric nanomolecules and administered through an intravenous route. It enhanced learning and memory capacities [116].
Solid Lipid Nanoparticles (SLNPs)
SLNPs enhanced drug retention in the brain area, raising absorption across the BBB [117]. Some of the drug’s effects are listed below.
Piperine drug is loaded on solid lipid nanomolecules through an intraperitoneal route inside the brain to decrease plaques and masses and to increase AChE enzyme activity [118].
- Huperzine A improved cognitive functions. No main irritation was detected in rat skin when the drug was loaded on SLNPs in an in vitro study [119].
In recent reports, the coating of SLNPs with polysorbate enhances drug bioavailabil- ity [120,121]. Some of the coated NPs are listed below. The drug clozapine was loaded on a Dynasan 116 [Tripalmitin] lipid matrix coated with surfactant Poloxamer 188, Epikuron 200 to unload the drug safely into the brain microenvironment [122,123].recognize ligands for interaction (Figure 3) [144].
Figure 3. Diagram showing the mechanism of targeted drug delivery across BBB in brain microenvi- ronment. Piperine loaded on SLNPs is injected intraperitonially, across BBB efferently to stop plaque formation. Polymeric nanomolecules are used for Tacrine delivery inside the brain, folic acid are loaded on the liposomes crossing blood–brain barrier to treat Alzheimer’s disease, while nanoemul- sions and SLNP are loaded with drugs used to deliver medicines inside the targeted brain area to cure Parkinson’s disease.
Advantages and Disadvantages of Nanomedicines
When employed for brain illnesses, nanomedicines have both benefits and drawbacks.
D. Nanocarriers Role in Major Cancers
a. Brain Cancer
Brain malignancy is the most critical disease in the sense of treatment [150]. Malig- nancies of the brain are most difficult to treat due to limits imposed by the blood–brain barrier [151]. The brain microvascular endothelium is present in the BBB and creates barri- ers that distinguish blood from the neural tissues of the brain [152]. The BBB prevents the entry of harmful toxins, xenobiotic and other metabolites from entering the brain [153]. The majority of brain cancers include glioma and glioblastoma. Both of these are among the most lethal forms of brain cancer [154]. The annual occurrence is 5.26 per 100,000 people or 17,000 new diagnoses each year. The most common treatment is radiation surgery and chemotherapy, usually implemented with with temozolomide (TMZ) [155]. Nanoparticles have a high potential to treat brain cancer because of their small size in nm, tissue-specific targeting properties, and ease in crossing the BBB [156].
b. Breast Cancer
Cancer causes major deaths all over the world. Tumors spread due to the proliferation of cells [171], which invade through the lymphatic system to various parts of the bodyif they becomes malignant [172]. According to WHO, the ratio of deaths globally due to cancer is assessed to be 13%, attributing 8.2 million deaths every year [173]. Breast cancer is the most recorded type of melanoma present in only females, and its severity leads to mortality more often than lung cancer [174]. In 2012, estimated female breast cancer cases were 1.7 million, with 25% of deaths all over the world [175]. In a recent study, a report published in the name of Global Cancer Statistics 2020: GLOBOCAN estimates the incidence and mortality worldwide for 36 cancers in 185 countries and provides an update on cancer internationally [176]. A reported estimate is 19.3 million new cancer cases (18.1 million excluding non-melanoma skin cancer) and almost 10 million cancer deaths(9.9 million without non-melanoma skin cancer) occurring in 2020 worldwide. Female breast cancer has exceeded lung cancer as the most frequently diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), prostate (7.3%), colorectal (10%), and stomach (5.6%) cancers [177]. For the effective treatment of breastcancer, surgery, chemotherapy, radiation therapy, hormonal therapy, and targeted therapy are performed [178]. However, nowadays, nanotechnology has gained interest for breast cancer treatment. Various organic and inorganic nanocarriers are used to deliver drugs to the specific target site [179]. Nanocarriers enhance the hydrophobicity of the anticancer drugs and promote specific target drug delivery [180]. Organic nanocarriers include polymeric nanocarriers, liposome nanocarriers, and solid lipid nanocarriers, while inorganic nanocarriers include magnetic nanocarriers, quantum dots, and carbon nanotubes (CNTs); both categories show great results towards treatment of heart diseases [181]. The mechanism of drug delivery in breast cancer is shown in Figure 4.
Figure 4. Schematic representation of mechanism of drug letrozol loaded on solid lipid nanomolecules (SLNs) and folic acid coupled to SLNs. The whole carrier was delivered inside the animal rat model to treat effects on breast cancer cell lines. Inside cytoplasm, biodegradation occurred, as well as drug release and caspases’ activation inside nucleus, causing apoptosis.
c. Lung Cancer
Lungs are basically responsible for inhalation [194]. The lung is composed airways (conveying the air inside and outside of the lungs) and alveoli (gas exchange zones) [195]. In fact, airways are comparatively tough barriers for particles to enter through, while the barrier along the alveolar wall and the capillaries is relatively fragile in the gas exchange component [196]. The huge exterior area of the alveoli and deep air blood exchange cause the alveoli to be less healthy when affected by environmental injuries. Such injuries may be the reason for some pulmonary illnesses, including lung malignancy [197]. Several nanomolecules are now being established for respiratory applications that aim at eliminating the restrictions of orthodox drugs [198]. Nanoparticles aid the cure of many lung diseases, such as asthma, tuberculosis, emphysema, cystic fibrosis, and cancer [199].
Drug Delivery Approach in Heart Diseases
Cardiovascular diseases include myocardial infraction (MI) [213], ischemic impair- ment, coronary artery disease (CAD), heart arrhythmias, pericardial disease, cardiomyopa- thy (heart muscle disease), and congenital heart disease [214,215]. All these illnesses are the basic main cause of mortality and morbidity in the world [216]. Cardiac diseases in humans involve incongruity in the morphogenesis of heart arrangement, functionality, and the healing and periodic shrinkage of cardiac muscles [217,218]. Around 50% of patients suffering from MI die within five years [216]. The insistence for a novel and effective remedy has brought about progress in direct drug carriage to the heart [219]. Modern therapeutic approaches have been developed to stop the incidence of heart failure after myocardial infarction [220]. Liposomes, silica NPs, dendrimers, cerium oxide NPs, micelles, TiO2 NPs, stents with nano-coatings, microbubbles, and polymer–drug conjugates are used for drug delivery. Magnetic nanomolecules like magnetoliposomes (MLs) are made up of the union of liposomes and magnetic nanomolecules. They are used as magnetic-targeted drug delivery [221]. The PEGylation of MLs increases their rate of flow in the blood, and pairing of the MLs with antibodies raises the rate of active target to pretentious positions [222]. Namdari and his co-workers performed experiments in a mice model afflicted with my- ocardial infraction (MI). Liposomes are used with various modifications and in different ways; they are adapted to load drugs on NPs for efficient delivery inside the cell. Cationic liposomes, perfluorocarbon nanomolecules, polyelectrolyte nanomolecules, and polymeric nanomolecules are the modified forms of nanocarriers [223]
- Drug Delivery Approach in Skin Diseases
Skin diseases are follicular and cutaneous. These dermatological diseases are treated nowadays with nanotechnology. Nanoparticle delivery for cutaneous disease treatment is preferred, with minor side effects. The conventionally used creams, gels, and ointments are insufficient for delivering drugs due to low penetration in skin tissues. To address this, polymeric, lipid, and surfactant nanocarriers are used. The polymeric micelles enhance drug penetration into the skin tissue to treat skin cancer. As in this reported study, chitosan polymeric NPs, liposomes, and gold nanomolecules can treat atopic dermatitis by improving drug penetration into the dermal and epidermal layers [246]. Gold nanomolecules are extremely small in size and can penetrate easily and effectively with very low toxicity and no skin damage. As such, they are used widely in nanocarrier formulations forskin diseases.
e. Drug Delivery Approach in Bone Diseases
Bone diseases includes bone defects due to many pathological factors, such as frac- ture, trauma, osteoporosis, arthritis, infections, and many other diseases. In fact, bone regeneration as a disease treatment is a very complex process, due to which nanomaterials and biological materials are fused to repair bones effectively. The combination of biomate- rial and nanomaterial has reduced bone implantation through the development of bone bioscaffolds [247].
Mechanism of Drug Delivery
The drugs encapsulated inside the nanoparticle is delivered through blood to the targeted area in the bones. The management of the sending nanomolecules as shown herenin (Figure 5).
Figure 5. Mechanism of nanomedicine delivery in bone diseases.
f. Drug Delivery Approach in Blood Diseases
There are various types of blood diseases, like hemopoietic blood disorder, as well as iron deficiency, leukemia, anemia, hemophilia, platelet diseases, and blood cancer. The conventionally used chemotherapeutic system causes damage to the immune system, with high risk of mortality. Bone marrow transplant is also an expensive and intricate process. For example, thalassemia is treated with deferoxamine, a chelating agent to treatexcessive iron in the blood. The siRNA-coated nanocomposite has the inhibitory activity for tumor cells in vivo [248]. The treatment of blood disorders with nanomedicine is stillunder investigation.
g. Future Challenges of Nanomedicines
In the field of nanomedicine, there are many innovations which show its importance in clinical and other medical aspects. Many scientists have investigated in their research how nanomedicine is involved in treating malignancies and reducing mortality and morbidity rates. However, there are also future challenges that nanomedicines have been facing until now [249]. The implementation of nanomedicine in clinical practice will face many issues with insurance companies, regulatory agencies, and the public health sector. Until now, the FDA has not developed any specific regulation for the products containing nanomaterials. Due to a lack of nanomaterial standardization and other safety issues, US agencies, such as the EPA and NIOSH, are giving less funding to these research endeavors. The opportunities of Nanotechnology include designing Nano sized, bio responsive systems which can diagnose and then deliver drugs to the site of location. Nanotechnology is an area which is changing vision of medical science. Nanotechnology includes characterization, production and application of nanoparticles in science fields [250]. They possess unique electrical, optical and biological properties. Many chemical and physical methods of synthesis have been reported in the literature [2-8]. Due to the ecofriendly nature of synthesis by biological methods, plant extracts, bacteria, algae, fungi and enzymes have also been exploited [8-23]. Biological methods for synthesizing of silver nanoparticles can be considered to be economical and sustainable alternative
to the existing chemical or physical methods. Designs of Nano robots include onboard sensors, power supplies, motors, manipulators and molecular computers. Nano robot is an excellent tool for future medicine. We can envision a day when you could inject billions of these Nano robots that would float around in your body. Nano robots could carry and deliver drugs into defected cells. These nano robots will be able to repair tissues, clean blood vessels and airways, transform our physiological capabilities and even potentially counter act the aging process. Nanotechnology as an emerging tool in medicinal applications especially for diabetes, arteriosclerosis, gene therapy, dentistry and cancer showed how actual developments in new manufacturing technologies are enabling innovative works which may help in constructing and employing nano robots most effectively for biomedical problems. Nano robots applied to medicine hold a wealth of promise from eradicating disease to reversing the aging process. Nano robots are also candidates for industrial applications. They will provide personalized treatments with improved efficacy and reduced side effects that are not available today. They will provide combined action drugs marketed with diagnostics, imaging agents acting as drugs, surgery with instant diagnostic feedback. The advent of molecular nanotechnology will again expand enormously the effectiveness, comfort and speed of future medical treatments while at the same time significantly reducing their risk, cost, and invasiveness. This science might sound like a fiction now, but nanorobotics has strong potential to revolutionize healthcare, to treat disease in future. It opens up new ways for vast, abundant research work. Nanotechnology will change health care and human life more profoundly than other developments. Consequently, they will change the shape of the industry, broadening the product development and marketing interactions between Pharma, Biotech, Diagnostic and Healthcare industries. In this review, Nanorobot’s mechanism and applications of them in medicine for curing diseases will be discussed.
A. Composition of Nanorobots
1. Biochip
Synthesis involves the joint use of Nano electronics, photolithography, and new biomaterials. It can be used for manufacturing of Nano robots for common medical applications, such as for surgical instrumentation, diagnosis and drug delivery. Electronics industries currently use biochips for manufacturing. Nano robots with biochips can be integrated in Nano electronics devices, which will allow tele-operation and advanced capabilities for medical instrumentation [8, 11].
- Bacteria Based
This approach uses biological microorganisms, like Escherichia coli bacteria. The model uses a flagellum for propulsion purposes. The use of electromagnetic fields is normally applied to control the motion of this kind of biological integrated device [8-9]
- Positional Nano Assembly
Robert Freitas and Ralph Merkle in 2000 are developing a practical research agenda specifically aimed at developing positional-controlled diamond mechanic synthesis and diamonded Nano factory that would be capable of building diamonded medical Nano robots.
- Nubots
Nubot is an abbreviation for "nucleic acid robots. “Nubots are synthetic robotics devices at the nanoscale. Representative Nubots include the several DNA walkers reported by Ned Seaman’s group at NYU, Niles Pierce's group at Caltech, John Reif's group at Duke University, Chengde Mao’s group at Purdue, and Andrew Turberfield's group at the University of Oxford [8, 9]
Advantages of Nanotechnology
- To cure HIV, Cancer, and other harmful diseases.
- Nano robots will restore lost tissue at the cellular level.
- Useful for monitoring, diagnosing and fighting sickness.
- Able to monitor neuro-electric signals and stimulate bodily systems.
C. Mechanism of Nanorobots
The research and development of Nano robots with embedded Nano biosensors and actuators is considered a new possibility to provide new medical devices for doctors. Controls are sought to effectively advance new medical technologies [22, 23]. Development of microelectronics in the 1980s has led to new tools for biomedical instrumentation [24, 25]. Further miniaturization towards integrated medical systems, providing efficient methodologies for pathological prognosis can be designed [26-28]. The use of micro devices in surgery and medical treatments is a reality which has brought many improvements in clinical procedures in recent years [29]. Catheterization has been successfully used as an important methodology for heart and intracranial surgery [30-32]. Now the advent of bimolecular science and new manufacturing techniques is helping us to advance the miniaturization of devices from micro to Nano electronics. Biomedical sensors are being operated by the latest technology which forms the basis for designing bimolecular actuators [33- 35]. A first series of nanotechnology prototypes for molecular machines are being investigated in different ways [18, 36-38], along with some devices for propulsion and sensing are also being studied by some workers [18, 36-39, 41] Nano robot Architecture: The medical Nano robot for biohazard defense should comprise a set of integrated circuit block as an ASIC (application-specific integrated circuit). The architecture has to address functionality for common medical applications [18], providing asynchronous interface for antenna, sensor, and a logic Nano processor, which is able to deliberate actuator and ultrasound communication activation when appropriate. The number of Nano devices to integrate a Nano robot should keep the same hardware sizes with regard to inside body operation applicability [3-6, 35, 47].
- Medical Applications of Nanorobots
Nano robots are expected to enable new treatments for patients suffering from different diseases, and will result in a remarkable advance in the history of medicine. Nanoparticles, liposomes and dendrimers are some nanomaterials being investigated for use in Nano medicine. Nanotechnology has provided the possibility of delivering drugs to specific cells using nanoparticles. Recent developments in the field of bimolecular computing have demonstrated the feasibility of processing logic tasks by biocomputers. Studies targeted at building biosensors and Nano-kinetic devices required to enable medical nanorobotics operation and locomotion, have also been progressing [38]. In recent years, the potential of nanotechnology has indeed motivated many governments to devote significant resources to this new field. The U.S. National Science Foundation has launched a program in “Scientific Visualization” in part to harness supercomputers in picturing the Nano world [3, 53]. In order to build electronics at nanoscales, firms are collaborating to produce new Nano products. Such companies include IBM, PARC, Hewlett Packard, Bell Laboratories, and Intel Corp. The use of Nano robots may advance biomedical intervention with minimally invasive surgeries and help patients who need constant body functions monitoring, or improve treatments efficiency through early diagnosis of possible serious diseases. For example, the Nano robots may be utilized to attach on transmigrating inflammatory cells or white blood cells, thus reaching inflamed tissues faster to assist in their healing process Nano robots will be applied in chemotherapy to combat cancer through precise chemical dosage administration, and a similar approach could be taken to enable Nano robots to deliver anti-HIV drugs [18-20, 54, 65]. Nano robots could be used to process specific chemical reactions in the human body as ancillary devices for injured organs. Monitoring diabetes and controlling glucose levels for patients will be a possible application of Nano robots. Nano robots might be used to see and break kidney stones. Another important possible feature of medical Nano robots will be the capability to locate atherosclerotic lesions in stenos blood vessels, particularly in the coronary circulation, and treat them either mechanically, chemically or pharmacologically. Cardiovascular problems are generally correlated with the obesity, human sedentary lifestyle, or hereditary characteristics [31, 43, and 61]
- Simulation
The use of micro devices in surgery and medical treatments is a reality which brought many improvements for clinical procedures in the last few years. For example, the catheterization has been used as an important methodology for many cardiology procedures in the same way as the development of micro technology [63] has lead on the 80’s to new tools for surgery, now nanotechnology will equally permit further advances providing better diagnosis, and new devices for medicine through the manufacturing of nanoelectronics [8-12]. Nano robots may be considered as the most suitable tool for specialists to solve several problems in medicine in the coming few year here including cardiology interventions and medical analyses. In our study, the Nano robot includes external sensors to inform it of collisions and to identify when it has encountered a chemical signal or abrupt changes of temperature for targeted areas. As a practical approach for medicine, thermal and chemical parameters from the patient’s body are used for the Nano robot activation. It is well known that there is significant temperature heterogeneity over inflamed plaque surfaces. They are typically hotter. The temperature difference at the site of the lesion from the core temperature can reach up to ~2ºC. Hence, in order to simulate various levels of inflammation, it was used for different wall temperatures in the atherosclerotic plaque region and the temperature distribution in the stenosed coronary artery was calculated. Significant temperature gradients were found in the recirculation zone, following the stenosis [52-55]. The Trans cardiac concentration gradient of some soluble adhesion molecules has been recently found to be correlative with the progression of coronary atherosclerosis. Therefore, their concentration in the blood vessel is also monitored, using a uniform distribution release from the plaque. In a similar manner, the concentrations of some specific proinflammatory cytokines is monitored, whose elevated concentrations are known as an evidence of formation of atherosclerotic lesions. The Nano robots swim in a near-wall region searching for the atherosclerotic lesion. The atherosclerotic lesion was reduced due to Nano robot’s activation. The parameters generated from the CFD simulation, namely velocities, temperature, signaling values, pro-inflammatory cytokines and soluble adhesion molecules concentrations, are transferred to the NCD [3, 5-7, 36] simulator to be included into the Nano robots operating environment [45- 47]. As the Nano robot should perform a pre-defined task in a specific target area, the trigger must be activated when the Nano robot is as close as possible to the target. The Nano robot motion takes the advantage of the blood flow velocity profile in such areas, which shows significantly lower velocities. Thus, the rapid activation could result in lower demand of energy. Optimization of control algorithms and activating triggers is the key for rapid behavior response in minimal energy cost. The optimal trigger values are defined running the Nano robots control programs. Therefore, the investigated stenos artery models provide important information useful to Nano robot manufacturing design in terms of sensors and actuators. The Nano robot’s activation goal is to decrease the artery occlusion.
- Nanorobotics in Dentistry
The growing interest in the future of dental applications of nanotechnology is leading to the emergence of a new field called Nano dentistry. Nano robots induce oral analgesia, desensitize tooth; manipulate the tissue to re-align and straighten irregular set of teeth and to improve durability of teeth. Further Nano robots can be used to do preventive, restorative and curative procedures [23-27]. Nano dental techniques involve many tissue engineering procedures for major tooth repair. Mainly nanorobotics manufacture and installation of a biologically autologous whole replacement tooth that includes both mineral and cellular components leading to complete dentition replacement therapy
- Tooth Durability and Appearance
Nano dentistry has given material that is nanostructured composite material, sapphire which increases tooth durability and appearance. Upper enamel layers are replaced by covalently bonded artificial material such as sapphire. This material has 100 to 200 times the hardness and failure strength than ceramic. Like enamel, sapphire is a somewhat susceptible to acid corrosion. Sapphire has best standard whitening sealant, cosmetic alternative. New restorative Nano material to increase tooth durability is Nanocomposites [32, 47, 64-66]. This is manufactured by Nano agglomerated discrete nanoparticles that are homogeneously distributed in resins or coatings to produce nanocomposites. The Nano filler include an alum inosilicate powder having a mean particle size of about 80 nm and a 1:4 ratio of alumina to silica. The Nano filler has a refractive index of 1.503, it has superior hardness, modulus of elasticity, translucency, esthetic appeal, excellent color density, high polish and 50% reduction in filling shrinkage. They are superior to conventional composites and blend with a natural tooth structure much better.
- Nano Impression
Impression material is available with nanotechnology application. Nano filler are integrated in the vinylpolysiloxanes, producing a unique addition siloxane impression material. The main advantage of material is it has better flow, improved hydrophilic properties hence fewer voids at margin and better model pouring, enhanced detail precision.
- Nano Robots for Brain Aneurysm For brain aneurysm prognosis, Nano robots need to track the vessel endothelial injury before a subarachnoid hemorrhage occurs. These changes on chemical concentration are used to guide the Nano robots to identify brain aneurysm in the early stages of development.
- Nanorobots in Cancer Detection and Treatment
Cancer can be successfully treated with current stages of medical technologies and therapy tools. However, a decisive factor to determine the chances for a patient with cancer to survives: how earlier it was diagnosed; what means, if possible, a cancer should be detected at least before the metastasis has begun. Another important aspect to achieve a successful treatment for patients is the development of efficient targeted drug delivery to decrease the side effects from chemotherapy [35, 38, 43-47]. Considering the properties of Nano robots to navigate as blood borne devices, they can help on such extremely important aspects of cancer therapy. Nano robots with embedded chemical biosensors can be used to perform detection of tumors cells in early stages of development inside the patient's body. Integrated Nano sensors can be utilized for such a task in order to find intensity of E-cadherin [62-64] signals. Therefore, a hardware architecture based on Nano bioelectronics is described for the application of Nano robots for cancer therapy. Analyses and conclusions for the proposed model are obtained through real time 3D simulation [22-27].
- Nanorobots in Gene Therapy Medical Nano robots can readily treat genetic diseases by comparing the molecular structures of both DNA and proteins found in the cell to known or desired reference structures [18-20, 64]. Any irregularities can then be corrected, or desired modifications can be edited in place. In some cases, chromosomal replacement therapy is more efficient than repair. Floating inside the nucleus of a human cell, an assembler-built repair vessel performs some genetic maintenance. Stretching a supercoil of DNA between its lower pair of robot arms, the Nano machine gently pulls the unwound strand through an opening for further analysis. Upper arms, meanwhile, detach regulatory proteins from the chain and place them in an intake port. The molecular structures of both DNA and proteins are compared to information stored in the database of a larger nano computer positioned outside the nucleus and connected to the cell repair ship by a communications link. Irregularities found in either structure are corrected and the proteins reattached to the DNA chain [56-58], which re-coils into its original form. With a diameter of only 50 nanometers, the repair vessel would be smaller than most bacteria and viruses, yet capable of therapies and cures well beyond the reach of present-day physicians. With trillions of these machines coursing through a patient’s blood stream, "internal medicine" would take on new significance. Disease would be attacked at the molecular level, and such maladies as cancer, viral infections and arteriosclerosis could be wiped out.
CONCLUSIONS
Nanotechnology-based nanomedicine is a diverse field for disease treatment. Nowa- days, in every sort of disease, nanotechnology is emerging as the best therapeutic to cure disease. At California University, researchers are developing methods to deliver cardiac stem cells to the heart. They attached nanovesicles that directly target injured tissue to increase the amount of stem cells there. Thus, the involvement of stem cells with nanotech- nology will develop many solutions for the disease-based queries in the medical arena. However, nanomedicine and nano drugs deal with many doubts. Irregularities and toxicity and safety valuations will be the topic of development in the future. Nanotechnology willbe in high demand. Nowadays, drug-targeted delivery through nanomolecules is catch- ing the attention of pharmaceutical researchers all over the world. Nanomedicine will overcome all the side effects of traditional medicines. This nanoscale technology will be incorporated in the medical system to diagnose, transport therapeutic drugs, and detect cancer growth, according to the National Cancer Institute. Experts are trying to treat SARS- CoV-2 with nanomedicine, as nanomolecules with 10–200 nm size can detect, for site- specific transfer, SARS-CoV-2, exterminate it, and improve the immune system of the body. Nanotechnology could help to combat COVID-19 by stopping viral contamination. Highly accurate nano-based sensors will be made in the future that will quickly recognize the virus and act by spraying to protect frontline doctors and the public. Furthermore, many antiviral disinfectants are being developed through nanobiotechnology to stop virus dissemination. In the future, nanotechnology will evolve to develop drugs with high activity, less toxicity, and sustained release to target tissue. Therefore, personalized medicine and nanomedicine both will be potential therapies to treat COVID-19 successfully, as well as to treat upcoming diseases in future.
REFERENCES
- Li, S.; Zhang, H.; Chen, K.; Jin, M.; Vu, S.H.; Jung, S.; He, N.; Zheng, Z.; Lee, M.S. Applicatio of chitosan/alginate nanoparticle in oral drug delivery systems: Prospects and challenges. Drug Deliv. 2022, 29, 1142–1149. [CrossRef] [PubMed]
- Vlachopoulos, A.; Karlioti, G.; Balla, E.; Daniilidis, V.; Kalamas, T.; Stefanidou, M.; Bikiaris, N.D.; Christodoulou, E.; Koumentakou, I.; Karavas, E.; et al. Poly (Lactic Acid)-Based Microparticles for Drug Delivery Applications: An Overview of Recent Advances. Pharmaceutics 2022, 14, 359. [CrossRef] [PubMed]
- Builders, P.F.; Arhewoh, M.I. Pharmaceutical applications of native starch in conventional drug delivery. Starch-Stärke 2016,9–10, 864–873. [CrossRef]
- Alshammari, M.K.; Alshehri, M.M.; Alshehri, A.M.; Alshlali, O.M.; Mahzari, A.M.; Almalki, H.H.; Kulaybi, O.Y.; Alghazwni, M.K.; Kamal, M.; Imran, M. Camptothecin loaded nano-delivery systems in the cancer therapeutic domains: A critical examination ofthe literature. J. Drug Deliv. Sci. Technol. 2022, 79, 104034. [CrossRef]
- Lai, H.; Liu, S.; Yan, J.; Xing, F.; Xiao, P. Facile Fabrication of Biobased Hydrogel from Natural Resources: L-Cysteine, Itaconic Anhydride, and Chitosan. ACS Sustain. Chem. Eng. 2020, 8, 4941– 4947. [CrossRef]
- Marco-Dufort, B.; Willi, J.; Vielba-Gomez, F.; Gatti, F.; Tibbitt, M.W. Environment Controls Biomolecule Release from Dynamic Covalent Hydrogels. Biomacromolecules 2021, 22, 146–157. [CrossRef]
- Smolensky, M.H.; Peppas, N.A. Chronobiology, drug delivery, and chronotherapeutics. Adv. Drug Deliv. Rev. 2018, 9–10, 828–851.
- Jamieson, L.E.; Byrne, H.J. Vibrational spectroscopy as a tool for studying drug-cell interaction: Could high throughput vibrational spectroscopic screening improve drug development. Vib. Spectrosc. 2017, 91, 16–30. [CrossRef]
- Mak, K.K.; Pichika, M.R. Artificial intelligence in drug development: Present status and future prospects. Drug Discov. Today 2019 24, 773–780. [CrossRef]
- Patra, J.K.; Das, G.; Fraceto, L.F.; Campos, E.V.R.; Rodriguez-Torres, M.D.P.; Acosta- Torres, L.S.; Diaz- Torres, L.A.; Grillo, R.; Swamy, M.K.; Sharma, S.; et al. Nano based drug delivery systems: Recent developments and future prospects. J. Nanobiotechnol. 2018, 16, 1–33. [CrossRef] [PubMed]
- Jain, K.K. Drug delivery systems—An overview. Drug Deliv. Syst. 2008, 437, 1–50.
- Ma, C.; Peng, Y.; Li, H.; Chen, W. Organ-on-a-Chip: A new paradigm for drug development. Trends Pharmacol. Sci. 2021, 42, 119–133. [CrossRef]
- Su, Y.; Xie, Z.; Kim, G.B.; Dong, C.; Yang, J. Design strategies and applications of circulating cell-mediated drug delivery systems. ACS Biomater. Sci. Eng. 2005, 4, 201–217. [CrossRef] [PubMed]
- Baig, N.; Kammakakam, I.; Falath, W. Nanomaterials: A review of synthesis methods, properties, recent progress, and challenges. Mater. Adv. 2021, 2, 1821–1871. [CrossRef]
- Prasad, R.D.; Charmode, N.; Shrivastav, O.P.; Prasad, S.R.; Moghe, A.; Sarvalkar, P.D.; Prasad, N.R. A review on concept ofnanotechnology in veterinary medicine. ES Food Agrofor. 2021, 4, 28–60. [CrossRef]
- Lateef, A.; Darwesh, O.M.; Matter, I.A. Microbial nanobiotechnology: The melting pot of microbiology, microbial technology andnanotechnology. In Microbial Nanobiotechnology; Springer: Singapore, 2021; pp. 1–19.
- Mansor, N.I.; Nordin, N.; Mohamed, F.; Ling, K.H.; Rosli, R.; Hassan, Z. Crossing the blood-brain barrier: A review on drugdelivery strategies for treatment of the central nervous system diseases. Curr. Drug Deliv. 2019, 16, 698–711. [CrossRef]Mughal, T.A.; Ali, S.; Hassan, A.; Kazmi, S.A.R.; Saleem, M.Z.; Shakir, H.A.; Nazer, S.; Farooq, M.A.; Awan,
- M.Z.; Khan, M.A.; et al. Phytochemical screening, antimicrobial activity, in vitro and in vivo antioxidant activity of Berberis lycium Royle root bark extract. Braz. J. Biol. 2021, 84. [CrossRef]
- Bonifácio, B.V.; da Silva, P.B.; dos Santos Ramos, M.A.; Negri, K.M.S.; Bauab, T.M.; Chorilli, M. Nanotechnology-based drug delivery systems and herbal medicines: A review. Int. J. Nanomed. 2014, 9, 1–15.
- Astruc, D. Introduction to Nanomedicine. Molecules 2016, 21, 4. [CrossRef]
- Peer, D.; Karp, J.M.; Hong, S.; Farokhzad, O.C.; Margalit, R.; Langer, R. Nanocarriers as an emerging platform for cancer therapy. Nano-Enabled Med. Appl. 2021, 61–91. [CrossRef]
- Cleal, K.; He, L.; Watson, P.D.; Jones, A.T. Endocytosis, intracellular traffic and fate of cell penetrating peptide-based conjugatesand nanomolecules. Curr. Pharm. Des. 2013, 19, 2878–2894. [CrossRef] [PubMed]
- Mirza, A.Z.; Siddiqui, F.A. Nanomedicine and drug delivery: A mini review. Int. Nano Lett. 2014, 4, 94. [CrossRef]
- Dizaj, S.M.; Jafari, S.; Khosroushahi, A.Y. A sight on the current nanoparticle-based gene delivery vectors. Nanoscale Res. Lett 2014, 9, 252. [CrossRef] [PubMed]
- Hussain, Z. Nanomedicines as emerging platform for simultaneous delivery of cancer therapeutics: New developments inovercoming drug resistance and optimizing anticancer efficacy. Artif. Cells Nanomed. Biotechnol. 2018, 46, 1015–1024. [CrossRef]
- Carmeliet, P.; Jain, R.K. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat. Rev.Drug Discov. 2011, 10, 417– 427. [CrossRef]
- Cho, H.-Y. Tumor homing reactive oxygen species nanoparticle for enhanced cancer therapy. ACS Appl. Mater. Interfaces 2019, 11, 23909–23918. [CrossRef]
- Dilnawaz, F.; Acharya, S.; Sahoo, S.K. Recent trends of nano-medicinal approaches in clinics. Int. J. Pharm. 2018, 538, 263–278.[CrossRef]
- Tran, S.; DeGiovanni, P.-J.; Piel, B.; Rai, P. Cancer nanomedicine: A review of recent success in drug delivery. Clin. Transl. Med.2017, 6, 1–21. [CrossRef]
- Cheng, R.; Meng, F.; Deng, C.; Klok, H.-A.; Zhong, Z. Dual and multi-stimuli responsive polymeric nanomolecules for programmed site-specific drug delivery. Biomaterials 2013, 34, 3647–3657. [CrossRef]
- Ge, Z.; Liu, S. Functional block copolymer assemblies responsive to tumor and intracellular microenvironments for site-specificdrug delivery and enhanced imaging performance. Chem. Soc. Rev. 2013, 42, 7289–7325. [CrossRef] [PubMed]
- Liu, Z.; Jiang, W.; Nam, J.; Moon, J.J.; Kim, B.Y. Immunomodulating nanomedicine for cancer therapy. Nano Lett. 2018, 18, 6655–6659. [CrossRef] [PubMed]
- Iyer, A.K.; Singh, A.; Ganta, S.; Amiji, M.M. Role of integrated cancer nanomedicine in overcoming drug resistance. Adv. DrugDeliv. Rev. 2013, 65, 1784–1802. [CrossRef] [PubMed]
- Torchilin, V.P. Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov. 005, 4, 145–160. [CrossRef]
- Couvreur, P.; Vauthier, C. Poly alkyl cyanoacrylate nanomolecules as drug carrier: Present state and perspectives. J. Control. Release1991, 17, 187–198. [CrossRef]
- Vauthier, C.; Dubernet, C.; Chauvierre, C.; Brigger, I.; Couvreur, P. Drug delivery to resistant tumors: The potential of poly (alkyl cyanoacrylate) nanomolecules. J. Control. Release 2003, 93, 151–160. [CrossRef]
- Shinto, Y.; Uchida, A.; Korkusuz, F.; Araki, N.; Ono, K. Calcium hydroxyapatite ceramic used as a delivery system for antibiotics.J. Bone Joint Surg. Br. 1992, 74, 600–604. [CrossRef]
- Esterhai, J.L., Jr.; Bednar, J.; Kimmelman, C.P. Gentamicin-induced ototoxicity complicating treatment of chronic osteomyelitis.Clin. Orthop. 1986, 209, 185–188. [CrossRef]
- Couvreur, P.; Puisieux, F. Nano-and microparticles for the delivery of polypeptides and proteins. Adv. Drug Deliv. Rev. 1993,10, 141–162. [CrossRef]
- Hwang, S.R.; Byun, Y. Advances in oral macromolecular drug delivery. Expert Opin. Drug Deliv. 2014, 11, 1955–1967. [CrossRef] [PubMed]
- Müller, J.J.; Lukowski, G.; Kröber, R.; Damaschun, G.; Dittgen, M. Acrylic acid copolymer nanomolecules for drug delivery: Structural characterization of nanomolecules by small-angle x-ray scattering. Colloid Polym. Sci. 1994, 272, 755–769. [CrossRef]
- Lukowski, G.; Müller, R.H.; Müller, B.W.; Dittgen, M. Acrylic acid copolymer nanomolecules for drug delivery. Part II: Charac- terization of nanomolecules surface-modified by adsorption of ethoxylated surfactants. Colloid Polym. Sci. 1993, 271, 100–105. [CrossRef]
- Fresta, M.; Puglisi, G.; Giammona, G.; Cavallaro, G.; Micali, N.; Furneri, P.M. Pefloxacine mesilate-and ofloxacin-loaded poly ethyl cyanoacrylate nanomolecules: Characterization of the colloidal drug carrier formulation. J. Pharm. Sci. 1995, 74, 895–902.[CrossRef]
- Cavallaro, G.; Fresta, M.; Giammona, G.; Puglisi, G.; Villari, A. Entrapment of ?-lactams antibiotics in polyethylcyanoacrylate nanomolecules: Studies on the possible in vivo application of this colloidal delivery system. Int. J. Pharm. 1994, 111, 31–41. [CrossRef]
- Pardridge, W.M. Physiologic-based strategies for protein drug delivery to the brain. J. Control. Release 996, 39, 281–286. [CrossRef]
- Partridge, W.M. Drug and gene targeting to the brain via blood–brain barrier receptor- mediated transport systems. Int. Congr. Ser 2005, 1277, 49–62. [CrossRef]
- Labhasetwar, V.; Song, C.; Levy, R.J. Nanoparticle drug delivery system for restenosis. Adv. Drug Deliv. Rev. 1997, 24, 63–85. [CrossRef]
- Labhasetwar, V.; Underwood, T.; Schwendeman, S.P.; Levy, R.J. Iontophoresis for modulation of cardiac drug delivery in dogs. Proc. Natl. Acad. Sci. USA 1995, 92, 2612–2616. [CrossRef]
- Kwon, G.S. Diblock copolymer nanomolecules for drug delivery. Crit. Rev. Ther. Drug Carr. Syst. 1998, 5, 481–512. [CrossRef]
- Kataoka, K.; Harada, A.; Nagasaki, Y. Block copolymer micelles for drug delivery: Design, characterization and biologicalsignificance. Adv. Drug Deliv. Rev. 2012, 64, 37–48. [CrossRef]
- Fernández-Urrusuno, R.; Calvo, P.; Remuñán-López, C.; Vila-Jato, J.L.; Alonso, M.J. Enhancement of nasal absorption of insulinusing chitosan nanomolecules. Pharm. Res. 1999, 16, 1576–1581. [CrossRef] [PubMed]
- Zhang, X.; Zhang, H.; Wu, Z.; Wang, Z.; Niu, H.; Li, C. Nasal absorption enhancement of insulin using PEG-grafted chitosannanomolecules. Eur. J. Pharm. Biopharm. 2008, 68, 526–534. [CrossRef] [PubMed]
- Kong, G.; Braun, R.D.; Dewhirst, M.W. Hyperthermia enables tumor-specific nanoparticle delivery: Effect of particle size. CancerRes. 2000, 60, 4440–4445. [PubMed]
- May, J.P.; Li, S.-D. Hyperthermia-induced drug targeting. Expert Opin. Drug Deliv. 2013, 10, 511–527. [CrossRef]
- Calvo, P. PEGylated poly cyanoacrylate nanomolecules as vector for drug delivery in prion diseases. J. Neurosci. Methods 2001, 111, 151–155. [CrossRef]
- Collinge, J. Molecular neurology of prion disease. J. Neurol. Neurosurg. Psychiatry 2005, 76, 906–919. [CrossRef]
- Qian, Z.M.; Li, H.; Sun, H.; Ho, K. Targeted drug delivery via the transferrin receptor- mediated endocytosis pathway. Pharmacol.Rev. 2002, 54, 561–587. [CrossRef]
- Ulbrich, K.; Hekmatara, T.; Herbert, E.; Kreuter, J. Transferrin-and transferrin- receptor- antibody6modified nanomolecules enabledrug delivery across the blood– brain barrier (BBB). Eur. J. Pharm. Biopharm. 2009, 71, 251–256. [CrossRef]
- Shankar, S.S.; Ahmad, A.; Pasricha, R.; Sastry, M. Bio reduction of chloroaurate ions by geranium leaves and its endophyticfungus yields gold nanomolecules of different shapes. J. Mater. Chem. 2003, 13, 1822–1826. [CrossRef]
- Panyam, J.; Labhasetwar, V. Targeting intracellular targets. Curr. Drug Deliv. 2004, 1, 235–247. [CrossRef
- Ashihara, H.; Suzuki, T. Distribution and biosynthesis of caffeine in plants. Front Biosci 2005, 9, 1864–7336. [CrossRef] [PubMed]
- Paciotti, G.F.; Kingston, D.G.; Tamarkin, L. Colloidal gold nanomolecules: A novel nanoparticle platform for developing multifunc-tional tumor-targeted drug delivery vectors. Drug Dev. Res. 2006, 67, 47–54. [CrossRef]
- Hattori, Y.; Maitani, Y. Folate-linked lipid-based nanoparticle for targeted gene delivery. Curr. Drug Deliv. 2005, 2, 243–252.[CrossRef] [PubMed]
- Lu, Y.; Low, P.S. Folate-mediated delivery of macromolecular anticancer therapeutic agents. Adv. Drug Deliv. Rev. 2002, 54, 675–693. [CrossRef]
- Xiao, S. Preparation of folate-conjugated starch nanomolecules and its application to tumor-targeted drug delivery vector. Chin. Sci.Bull. 2006, 51, 1693–1697. [CrossRef]
- Yu, D.; Xiao, S.; Tong, C.; Chen, L.; Liu, X. Dialdehyde starch nanomolecules: Preparation and application in drug carrier. Chin. Sci.Bull. 2007, 52, 2913–2918. [CrossRef]
- Han, G.; Ghosh, P.; Rotello, V.M. Multi-Functional Gold Nanoparticles for Drug Delivery. In Bio- Applications of Nanoparticles; Chan, W.C.W., Ed.; Springer: New York, NY, USA, 2007; pp. 48–56.
- Ghosh, P.; Han, G.; De, M.; Kim, C.K.; Rotello, V.M. Gold nanomolecules in delivery applications. Adv. Drug Deliv. Rev. 2008, 60, 1307–1315. [CrossRef]
- Kim, H.S.; Lee, D.Y. Near-infrared-responsive cancer photothermal and photodynamic therapy using gold nanomolecules. Polymers 2018, 10, 961. [CrossRef]
- Cheng, Y.; Samia, A.C.; Meyers, J.D.; Panagopoulos, I.; Fei, B.; Burda, C. Highly efficient drug delivery with gold nanoparticlevectors for in vivo photodynamic therapy of cancer. J. Am. Chem. Soc. 2008, 130, 10643–10647. [CrossRef] [PubMed]
- Gazori, T.; Khoshayand, M.R.; Azizi, E.; Yazdizade, P.; Nomani, A.; Haririan, I. Evaluation of Alginate/Chitosan nanomolecules asantisense delivery vector: Formulation, optimization and in vitro characterization. Carbohydr. Polym. 2009, 77, 599–606. [CrossRef]
- Sarmento, B.; Ribeiro, A.J.; Veiga, F.; Ferreira, D.C.; Neufeld, R.J. Insulin-loaded nanomolecules are prepared by alginate ionotropicpre-gelation followed by chitosan polyelectrolyte complexation. J. Nanosci. Nanotechnol. 2007, 7, 2833–2847. [CrossRef] [PubMed]
- Rosenholm, J.M.; Peuhu, E.; Bate-Eya, L.T.; Eriksson, J.E.; Sahlgren, C.; Lindén, M. Cancer-Cell-Specific Induction of ApoptosisUsing Mesoporous Silica Nanoparticles as Drug-Delivery Vectors. Small 2010, 6, 1234–1241. [CrossRef] [PubMed] Kohler, N.; Sun, C.; Wang, J.; Zhang, M. Methotrexate-modified superparamagnetic nanomolecules and their intracellular uptakeinto human cancer cells. Langmuir 2005, 21, 8858–8864. [CrossRef]
- Alhaddad, A. Nanodiamond as a vector for siRNA delivery to Ewing sarcoma cells. Phys. Q.-Bio. 2011, 21, 3087–3095. [CrossRef] [PubMed]
- Mengesha, A.E.; Youan, B.C. Nano diamonds for drug delivery systems. In Diamond- Based Materials for Biomedical Applications;Elsevier: Amsterdam, The Netherlands, 2013; pp. 186–205.
- Arjunan, N.K.; Murugan, K.; Rejeeth, C.; Madhiyazhagan, P.; Barnard, D.R. Green Synthesis of Silver Nanoparticles for theControl of Mosquito Vectors of Malaria, Filariasis, and Dengue. Vector-Borne Zoonotic Dis. 2012, 12, 262–268. [CrossRef]
- Jadoun, S.; Arif, R.; Jangid, N.K.; Meena, R.K. Green synthesis of nanomolecules using plant extracts: A review. Environ. Chem. Lett. 2021, 19, 355–374. [CrossRef]
- Brown, P.K.; Qureshi, A.T.; Moll, A.N.; Hayes, D.J.; Monroe, W.T. Silver Nanoscale Antisense Drug Delivery System forPhotoactivated Gene Silencing. ACS Nano 2013, 7, 2948–2959. [CrossRef]
- Minelli, C.; Lowe, S.B.; Stevens, M.M. Engineering nanocomposite materials for cancer therapy. Small 2010, 21, 2336–2357.[CrossRef]
- Rajeshkumar, S. Synthesis of silver nanomolecules using fresh bark of Pongamia pinnata and characterization of its antibacterialactivity against gram positive and gram negative pathogens. Resour.-Effic. Technol. 2016, 2, 30–35. [CrossRef]
- Beg, M. Green synthesis of silver nanomolecules using Pongamia pinnata seed: Characterization, antibacterial property, andspectroscopic investigation of interaction with human serum albumin. J. Mol. Recognit. 2017, 30, e2565. [CrossRef] [PubMed]
- Urbán, P.; Ranucci, E.; Fernàndez-Busquets, X. Polyamidoamine nanomolecules as nanocarriers for the drug delivery to malariaparasite stages in the mosquito vector. Nanomed 2015, 10, 3401–3414. [CrossRef] [PubMed]
- Chamundeeswari, M.; Jeslin, J.; Verma, M.L. Nanocarriers for drug delivery applications. Environ. Chem. Lett. 2019, 17, 849–865.[CrossRef]
- Kulbacka, J. Electroporation and lipid nanomolecules with cyanine IR-780 and flavonoids as efficient vectors to enhanced drugdelivery in colon cancer. Bioelectrochemistry 2016, 110, 19–31. [CrossRef]
- Lamichhane, T.N.; Raiker, R.S.; Jay, S.M. Exogenous DNA loading into extracellular vesicles via electroporation is size-dependentand enables limited gene delivery. Mol. Pharm. 2015, 12, 3650– 3657. [CrossRef]
- Ju, Z.; Sun, W. Drug delivery vectors based on filamentous bacteriophages and phage- mimetic nanomolecules. Drug Deliv. 2017 24, 1898–1908. [CrossRef]
- Jahromi, M.A.M.; Zangabad, P.S.; Basri, S.M.M.; Zangabad, K.S.; Ghamarypour, A.; Aref, A.R. Recent progress in targeted deliveryvectors based on biomimetic nanomolecules. Signal Transduct. Target. Ther. 2021, 6, 225.
- Aljabali, A.A. Innovative Applications of Plant Viruses in Drug Targeting and Molecular Imaging—A Review. Curr. Med. Imaging 2021, 17, 491–506. [CrossRef]
- Slita, A.; Egorova, A.; Casals, E.; Kiselev, A.; Rosenholm, J.M. Characterization of modified mesoporous silica nanomolecules asvectors for siRNA delivery. Asian J. Pharm. Sci. 2018, 13, 592–599. [CrossRef]
- Wu, S.H.; Mou, C.Y.; Lin, H.P. Synthesis of mesoporous silica nanomolecules. Chem. Soc. Rev. 2013, 42, 3862–3875. [CrossRef] [PubMed]
- Garg, U.; Chauhan, S.; Nagaich, U.; Jain, N. Current Advances in Chitosan Nanoparticles Based Drug Delivery and Targeting. Adv. Pharm. Bull. 2019, 9, 195–204. [CrossRef]
- Pathak, C.; Vaidya, F.U.; Pandey, S.M. Mechanism for development of nanobased drug delivery system. Appl. Target. Nano DrugsDeliv. Syst. 2019, 1, 35–67.
- Ghaz-Jahanian, M.A.; Abbaspour-Aghdam, F.; Anarjan, N.; Berenjian, A.; Jafarizadeh- Malmiri, H. Application of chitosan-basednanocarriers in tumor- targeted drug delivery. Mol. Biotechnol. 2015, 157, 201–218. [CrossRef] [PubMed]
- Assa, F. Chitosan magnetic nanomolecules for drug delivery systems. Crit. Rev. Biotechnol. 2017, 37, 492–509. [CrossRef]
- Li, Y.; Wang, S.; Song, F.X.; Zhang, L.; Yang, W.; Wang, H.X. A pH-sensitive drug delivery system based on folic acid-targeted HBP-modified mesoporous silica nanomolecules for cancer therapy. Colloids Surf. Physicochem. Eng. Asp. 2020, 590, 124470. [CrossRef]
- Shafiei, N.; Nasrollahzadeh, M.; Iravani, S. Green Synthesis of Silica and Silicon Nanoparticles and Their Biomedical and Catalytic Applications. Comments Inorg. Chem. 2021, 41, 317–372. [CrossRef]
- Shariatinia, Z. Inorganic Material-Based Nanocarriers for Delivery of Biomolecules. Nanoeng. Biomater. Biomed. Appl. 2022, 2, 245–293.
- Ho, W.; Gao, M.; Li, F.; Li, Z.; Zhang, X.; Xu, X. Next-Generation Vaccines: Nanoparticle-Mediated DNA and mRNA Delivery. Adv. Healthc. Mater. 2021, 10, 2001812. [CrossRef]
- Thi, T.T.; Suys, E.J.; Lee, J.S.; Nguyen, D.H.; Park, K.D.; Truong, N.P. Lipid-based nanomolecules in the clinic and clinical trials: From cancer nanomedicine to COVID- 19 vaccines. Vaccines 2021, 9, 359. [CrossRef]
- Mallakpour, S.; Azadi, E.; Hussain, C.M. The latest strategies in the fight against the COVID-19 pandemic: The role of metal andmetal oxide nanomolecules. New J. Chem. 2021, 45, 6167–6179. [CrossRef]
- Kelleni, M.T. Resveratrol-zinc nanomolecules or pterostilbene-zinc: Potential COVID- 19 mono and adjuvant therapy. Biomed. Pharmacother. 2021, 139, 111626. [CrossRef] [PubMed]
- Zhang, H.; Zhang, L.; Zhong, H.; Niu, S.; Ding, S.; Lv, S. Iridium oxide nanomolecules - based theranostic probe for in vivo tumor imaging and synergistic chem/photothermal treatments of cancer cells. Chem. Eng. J. 2022, 430, 132–675. [CrossRef]
- Cao, S.; Deng, Y.; Zhang, L.; Aleahmad, M. Chitosan nanomolecules, as biological macromolecule- based drug delivery systems to improve the healing potential of artificial neural guidance channels: A review. Int. J. Biol. Macromol. 2022, 201, 569– 579. [CrossRef]
- Fricke, I.B.; Schelhaas, S.; Zinnhardt, B.; Viel, T.; Hermann, S.; Couillard-Després, S.; Jacobs, A.H. In vivo bioluminescence imaging of neurogenesis—The role of the blood brain barrier in an experimental model of Parkinson’s disease. Eur. J. Neurosci. 2017, 45, 975–986. [CrossRef]
- Komarova, Y.A.; Kruse, K.; Mehta, D.; Malik, A.B. Protein Interactions at Endothelial Junctions and Signaling Mechanisms Regulating Endothelial Permeability. Circ. Res. 2017, 120, 179–206. [CrossRef]
- Stamatovic, S.M.; Keep, R.F.; Andjelkovic, A.V. Brain endothelial cell-cell junctions: How to ‘open’ the blood brain barrier. Curr. Neuropharmacol. 2008, 6, 179–192. [CrossRef]
- Sahni, J.K.; Doggui, S.; Ali, J.; Baboota, S.; Dao, L.; Ramassamy, C. Neurotherapeutic applications of nanomolecules in Alzheimer’s disease. J. Control. Release 2012, 152, 208–
- 231. [CrossRef]
- Naz?rog? lu, M.; Muhamad, S.; Pecze, L. Nanoparticles as potential clinical therapeutic agents in Alzheimer’s disease: Focus on selenium nanomolecules. Expert Rev. Clin. Pharmacol. 2017, 16, 73– 782. [CrossRef]
- Kaur, I.P.; Bhandari, R.; Bhandari, S.; Kakkar, V. Potential of solid lipid nanomolecules in brain targeting. J. Control. Release 2008,
- 127, 97–109. [CrossRef]
- Alam, M.I.; Beg, S.; Samad, A.; Baboota, S.; Kohli, K.; Ali, J.; Ahuja, A.; Akbar, M. Strategy for effective brain drug delivery. Eur. J. Pharm. Sci. 2010, 40, 385–403. [CrossRef] [PubMed]
- Chen, Y.; Wei, C.; Lyu, Y.; Chen, H.; Jiang, G.; Gao, X. Biomimetic drug-delivery systems for the management of brain diseases.
- Biomater. Sci. 2020, 8, 1073–1088. [CrossRef] [PubMed]
- Kreuter, J. Nanoparticles system for brain delivery of drugs. Adv. Drug Deliv. Rev. 2001,
- 47, 65–81. [CrossRef] [PubMed]
- Chen, Y.; Dalwadi, G.; Benson, H.A.E. Drug delivery across the blood—Brain barrier. Cur. Drug Deliv 2004,
- 1, 361–376. [CrossRef] [PubMed]
- Fundaro, A.; Cavalli, R.; Bagoni, A.; Vighetto, D.; Zara, G.P.; Gasco, M.R. Non-stealth and stealth solid lipid nanomolecules(sln) carrying doxorubicin: Pharmacokinetic and tissue distribution after IV administration to rats. Pharm. Res. 2000, 42, 337–343. [CrossRef] [PubMed]
- Venkateshwarlu, V.; Manjunath, K. Preparation, characterization and in vitro release kinetics of clozapine Solid Lipid Nanoparti- cles. J. Control. Release 2004, 65, 627–638. [CrossRef] [PubMed]
- Olbrich, C.; Kayser, O.; Muller, R.H. Lipase degradation of Dynasan 114 S 116 SLN-effect of surfactant, storage time S crystallinity.
- Int. J. Pharm. 2002, 237, 119–128.
- Cavalli, R.; Caputo, O.; Carlotti, M.E.; Trotta, M.; Scarnecchia, C.; Gasco, M.R. Sterilization and freeze drying of drug-free anddrug-loaded solid lipid nanomolecules. Int. J. Pharm. 1997, 148, 47–54. [CrossRef]
- Jenning, V.; Gysler, A.; Schäfer-Korting, M.; Gohla, S.H. Vitamin A loaded solid lipid nanomolecules for topical use: Occlusiveproperties and drug targeting to the upper skin. Eur. J. Pharm. Biopharm. 2000, 49, 211–218. [CrossRef]
- Olbrich, C.; Gessner, A.; Schroder, W.; Kayser, O.; Muller, R.H. Lipid drug conjugate nanomolecules of the hydrophilic drugdiminazine-cytotoxicity testing and mouse serum adsorption. J. Control. Release 2004, 96, 425–435. [CrossRef]
-
- Schwarz, C.; Mehnert, W.; Lucks, J.S.; Muller, R.H. Solid lipid nanomolecules for controlled drug delivery. I. Production, characterization and sterilization. J. Control. Release 1994, 96, 83–96. [CrossRef]
- Zimmermann, E.; Müller, R.H.; Mader, K. Influence of different parameters on reconstitution of lyophilized SLN. Int. J. Pharm.
- 2000, 196, 211–213. [CrossRef] [PubMed]
- Kreuter, J. Physicochemical characterization of polyacrylic nanomolecules. Int. J. Pharm.
- 1983, 65, 43–58. [CrossRef]
- Wissing, S.A.; Kayser, O.; Müller, R.H. Solid lipid nanomolecules for parenteral drug delivery. Adv. Drug Deliv. Rev. 2004,
- 56, 1257–1272. [CrossRef] [PubMed]
- Müller, R.H.; Rühl, D.; Runge, S.A. Biodegradation of solid lipid nanomolecules as a function of lipase incubation time. Int. J. Pharm. 1996, 144, 115–121. [CrossRef]
- Lai, F.; Fadda, A.M.; Sinico, C. Liposomes for brain delivery. Expert Opin. Drug Deliv. 2013,
- 10, 1003–1022. [CrossRef]
- Samad, A.; Sultana, Y.; Aqil, M. Liposomal drug delivery systems: An update review.
- Curr. Drug Deliv. 2007, 4, 297–305. [CrossRef]
- Leonor Pinzon-Daza, M.; Campia, I.; Kopecka, J.; Garzón, R.; Ghigo, D.; Rigant, C. Nanoparticle-and liposome-carried drugs: New strategies for active targeting and drug delivery across blood-brain barrier. Curr. Drug Metab. 2013, 14, 625–640. [CrossRef]
- Gharbavi, M.; Amani, J.; Kheiri-Manjili, H.; Danafar, H.; Sharafi, A. Niosome: A promising nanocarrier for natural drug delivery through blood-brain barrier. Adv. Pharmacol. Sci. 2018, 2018, 6847971. [CrossRef]
- Bhattamisra, S.K.; Shak, A.T.; Xi, L.W.; Safian, N.H.; Choudhury, H.; Lim, W.M.; Shahzad, N.; Alhakamy, N.A.; Anwer, M.K.; Radhakrishnan, A.K.; et al. Nose to brain delivery of rotigotine loaded chitosan nanomolecules in human SH-SY5Y neuroblastoma cells and animal model of Parkinson’s disease. Int. J. Pharm. 2020, 579, 119148. [CrossRef]
- Fan, Y.; Chen, M.; Zhang, J.; Maincent, P.; Xia, X.; Wu, W. Updated Progress of Nanocarrier-Based Intranasal Drug Delivery Systems for Treatment of Brain Diseases. Crit. Rev. Ther. Drug Carr. Syst. 2018, 5, 433–467. [CrossRef] [PubMed]
- Li, X.; Tsibouklis, J.; Weng, T.; Zhang, B.; Yin, G.; Feng, G.; Cui, Y.; Savina, I.N.; Mikhalovska, L.I.; Sandeman, S.R.; et al. Nanocarriers for drug transport across the blood–brain barrier. J. Drug Target. 2017, 25, 17–28. [CrossRef]
- Majumder, J.; Taratula, O.; Minko, T. Nanocarrier-based systems for targeted and site- specific therapeutic delivery. Adv. DrugDeliv. Rev. 2018, 144, 57–77. [CrossRef
- Jogani, V.V.; Shah, P.J.; Mishra, P.; Mishra, A.K.; Misra, A.R. Intranasal Mucoadhesive Microemulsion of Tacrine to Improve BrainTargeting. Alzheimer Dis. Assoc. Disord. 2008, 22, 116–124. [CrossRef
- Chaiyana, W.; Rades, T.; Okonogi, S. Characterization and in vitro permeation study of microemulsions and liquid crystalline systems containing the anticholinesterase alkaloidal extract from Tabernaemontana divaricata. Int. J. Pharm. 2013, 452, 201–210. [CrossRef]
- Hayes, M.T. Parkinson’s disease and parkinsonism. Am. J. Med. 2019, 132, 802–807. [CrossRef]
- Ishihara, L.; Brayne, C. A systematic review of depression and mental illness preceding Parkinson’s disease. Acta Neurol. Scand. 2006, 113, 211–220. [CrossRef]
- Kyle, S.; Saha, S. Nanotechnology for the detection and therapy of stroke. Adv. Healthc. Mater. 2014, 3, 1703–1720. [CrossRef]
- Ghazy, E.; Rahdar, A.; Barani, M.; Kyzas, G.Z. Nanomaterials for Parkinson disease: Recent progress. J. Mol. Struct. 2021, 1231, 129698. [CrossRef]
- Dudhipala, N.; Gorre, T. Neuroprotective Effect of Ropinirole Lipid Nanoparticles Enriched Hydrogel for Parkinson’s Disease: InVitro, Ex Vivo, Pharmacokinetic and Pharmacodynamic Evaluation. Pharmaceutics 2020, 12, 448. [CrossRef] [PubMed]
- Barcia, E.; Boeva, L.; García-García, L.; Slowing, K.; Fernández-Carballido, A.; Casanova, Y. Nanotechnology-based drug deliveryof ropinirole for Parkinson’s disease. Drug Deliv. 2017, 24, 1112–1123. [CrossRef] [PubMed]
- Cacciatore, I.; Ciulla, M.; Fornasari, E.; Marinelli, L.; Di Stefano, A. Solid lipid nanomolecules as a drug delivery system for thetreatment of neurodegenerative diseases. Expert Opin. Drug Deliv. 2016, 13, 1121–1131. [CrossRef]
- Jha, A.; Mukhopadhaya, K. Supporting Diagnosis and Treatment. In Alzheimer’s Disease; Springer: Berlin/Heidelberg, Germany, 2021; pp. 65–85
- McMahon, D.; O’Reilly, M.A.; Hynynen, K. Therapeutic Agent Delivery across the Blood– Brain Barrier Using Focused Ultrasound. Annu. Rev. Biomed. Eng. 2021, 23, 89–113. [CrossRef]
- Bhaskar, S.; Tian, F.; Stoeger, T.; Kreyling, W.; de la Fuente, J.M.; Grazú, V. Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: Perspectives on tracking and neuroimaging. Part. Fibre Toxicol. 2010, 7, 3. [CrossRef]
- Saraiva, C.; Praça, C.; Ferreira, R.; Santos, T.; Ferreira, L.; Bernardino, L. Nanoparticle- mediated brain drug delivery: Overcoming blood–brain barrier to treat neurodegenerative diseases. J. Control. Release 2016, 235, 34–47. [CrossRef]
- Mendez, G.; Ozpinar, A.; Raskin, J.; Gultekin, S.H.; Ross, D.A. Case comparison and literature review of glioblastoma: A tale of two tumors. Surg. Neurol. Int. 2014, 5, 121.
- Omuro, A.; DeAngelis, L.M. Glioblastoma and Other Malignant Gliomas: A Clinical Review. JAMA 2013, 310, 1842–1850. [CrossRef
- Zhao, Z.; Ukidve, A.; Kim, J.; Mitragotri, S. Targeting strategies for tissue-specific drug delivery. Cell 2020, 181, 151–167. [CrossRef]
- Prasad, B.L.V. Cytotoxicity of sophorolipid -gellan gum- gold nanoparticle conjugates and their doxorubicin loaded derivativestowards human glioma and human glioma stem cell lines. Nanoscale 2011, 3, 575–580.
- Mazur, J.; Roy, K.; Kanwar, J.R. Recent advances in nanomedicine and survivin targeting in brain cancers. Nanomedicine 2018, 13, 105–137. [CrossRef] [PubMed]
- Wan, X.; Zheng, X.; Pang, X.; Pang, Z.; Zhao, J.; Zhang, Z. Lapatinib-loaded human serum albumin nanomolecules for the prevention and treatment of triple-negative breast cancer metastasis to the brain. Oncotarget 2016, 7, 34038–34051. [CrossRef] [PubMed]
- Erin, N.; Kale, S¸.; Tanr?över, G.; Köksoy, S.; Duymus¸, Ö.; Korcum, A.F. Differential characteristics of heart, liver, and brain metastatic subsets of murine breast carcinoma. Breast Cancer Res. Treat 2013, 139, 677–689. [CrossRef] [PubMed]
- Gao, H.; Yang, Z.; Cao, S.; Xi, Z.; Zhang, S.; Pang, Z. Behavior and anti-glioma effect of lapatinib- incorporated lipoprotein-likenanomolecules. Nanotechnology 2012, 23, 435101. [CrossRef] [PubMed]
- Bonde, G.V.; Yadav, S.K.; Chauhan, S.; Mittal, P.; Ajmal, G.; Thokala, S.; Mishra, B. Lapatinib nano- delivery systems: A promisingfuture for breast cancer treatment. Expert Opin. Drug Deliv. 2018, 15, 495–507. [CrossRef] [PubMed]
- Ghorbani, M.; Bigdeli, B.; Jalili-baleh, L.; Baharifar, H.; Akrami, M.; Dehghani, S. Curcumin-lipoic acid conjugate as a promising anticancer agent on the surface of gold- iron oxide nanocomposites: A pH- sensitive targeted drug delivery system for brain cancer theranostics. Eur. J. Pharm. Sci. 2018, 114, 175–188. [CrossRef] [PubMed]
- Kim, E.H.; Sohn, S.; Kwon, H.J.; Kim, S.U.; Kim, M.J.; Lee, S.J.; Choi, K.S. Sodium selenite induces superoxide-mediated mitochondrial damage and subsequent autophagic cell death in malignant glioma cells. Cancer Res. 2007, 67, 6314–6324. [CrossRef]
- Agrawal, P.; Singh, R.P.; Sonali; Kumari, L.; Sharma, G.; Koch, B. TPGS-chitosan cross- linked targeted nanomolecules for effectivebrain cancer therapy. Mater. Sci. Eng. C 2017, 74, 167–176. [CrossRef]
- Muthu, M.S.; Avinash Kulkarni, S.; Liu, Y.; Feng, S.-S. Development of docetaxel- loaded vitamin E TPGS micelles: Formulationoptimization, effects on brain cancer cells and biodistribution in rats. Nano Diam. 2012, 7, 353–364. [CrossRef]
- Lara-Velazquez, M.; Alkharboosh, R.; Norton, E.S.; Ramirez-Loera, C.; Freeman, W.D.; Guerrero- Cazares, H. Chitosan-Based Non-viral Gene and Drug Delivery Systems for Brain Cancer. Front. Neurol. 2020, 11, 740. [CrossRef] [PubMed]
- Denora, N.; Trapani, A.; Laquintana, V.; Lopedota, A.; Trapani, G. Recent advances in medicinal chemistry and pharmaceuticaltechnology-strategies for drug delivery to the brain. Curr. Top. Med. Chem. 2009, 9, 182–196. [CrossRef] [PubMed]
- Shinde, G.; Shiyani, S.; Shelke, S.; Chouthe, R.; Kulkarni, D.; Marvaniya, K. Enhanced brain targeting efficiency using 5-FU(fluorouracil) lipid–drug conjugated nanomolecules in brain cancer therapy. Prog. Biomater. 2020, 9, 259–275. [CrossRef] [PubMed]
- Arias, J.L.; Clares, B.; Morales, M.E.; Gallardo, V.; Ruiz, M.A. Lipid-based drug delivery systems for cancer treatment. Curr. DrugTargets 2011, 12, 1151–1165. [CrossRef]
- Folkman, J. Role of angiogenesis in tumor growth and metastasis. Semin. Oncol. 2002, 29, 15–18. [CrossRef]
- Wicki, A.; Witzigmann, D.; Balasubramanian, V.; Huwyler, J. Nanomedicine in cancer therapy: Challenges, opportunities, andclinical applications. J. Control. Release 2015, 200, 138–157. [CrossRef]
- Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates ofincidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394–424. [CrossRef]
- Dey, S.; Soliman, A.S. Cancer in the global health era: Opportunities for the Middle East and Asia. Asia Pac. J. Public Health 2010, 22, 75S–82S. [CrossRef]
- Torre, L.A.; Bray, F.; Siegel, R.L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin. 2015, 65, 87–108. [CrossRef]
- Çelikgün, S.; Koç, T.; Tuncer, E.; Özer, H.; Nur, N. Cancer Map between 2010–2019 Sivas City. Int. J. Acad Med. Pharm. 2021, 3, 273–276. [CrossRef]
- Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2020, 71, 209–249. [CrossRef] [PubMed]
- Jin, K.-T.; Lu, Z.-B.; Chen, J.-Y.; Liu, Y.-Y.; Lan, H.-R.; Dong, H.-Y. Recent trends in nanocarrier-based targeted chemotherapy: Selective delivery of anticancer drugs for effective lung, colon, cervical, and breast cancer treatment. J. Nanomater. 2020, 2020, 9184284. [CrossRef]
- Biswas, S.; Kumari, P.; Lakhani, P.M.; Ghosh, B. Recent advances in polymeric micelles for anti-cancer drug delivery. Eur. J. Pharm. Sci. 2016, 83, 184–202. [CrossRef] [PubMed]
- Lee, J.J.; Saiful Yazan, L.; Che Abdullah, C.A. A review on current nanomaterials and their drug conjugate for targeted breast cancer treatment. Int. J. Nanomed. 2017, 12, 2373–2384. [CrossRef] [PubMed]
- Yassemi, A.; Kashanian, S.; Zhaleh, H. Folic acid receptor-targeted solid lipid nanomolecules to enhance cytotoxicity of letrozole through induction of caspase-3 dependent-apoptosis for breast cancer treatment. Pharm. Dev. Technol. 2020, 25, 397–407. [CrossRef] [PubMed]
- Chen, Q.; Zheng, J.; Yuan, X.; Wang, J.; Zhang, L. Folic acid grafted and tertiary amino based pH- responsive pentablock polymeric micelles for targeting anticancer drug delivery. Mater. Sci. Eng. 2018, 82, 1–9. [CrossRef]
- Chen, Y.; Tezcan, O.; Li, D.; Beztsinna, N.; Lou, B.; Etrych, T.; Ulbrich, K.; Metselaar, J.M.; Lammers, T.; Hennink, W.E. Overcoming multidrug resistance using folate receptor- targeted and pH-responsive polymeric nanogels containing covalently entrapped doxorubicin. Nanoscale 2017, 9, 10404–10419. [CrossRef]
- Fathy Abd-Ellatef, G.-E.; Gazzano, E.; Chirio, D.; Ragab Hamed, A.; Belisario, D.C.; Zuddas, C. Curcumin-Loaded Solid Lipid Nanoparticles Bypass P-Glycoprotein Mediated Doxorubicin Resistance in Triple Negative Breast Cancer Cells. Pharmaceutics2020, 12, 96. [CrossRef
- Wang, W.; Chen, T.; Xu, H.; Ren, B.; Cheng, X.; Qi, R.; Liu, H.; Wang, Y.; Yan, L.; Chen, S.; et al. Curcumin-loaded solid lipid nanomolecules enhanced anticancer efficiency in breast cancer. Molecules 2018, 12, 1578. [CrossRef]
- Riganti, C.; Gazzano, E.; Gulino, G.R.; Volante, M.; Ghigo, D.; Kopecka, J. Two repeated low doses of doxorubicin are more effective than a single high dose against tumors overexpressing P- glycoprotein. Cancer Lett. 2015, 23, 219–226. [CrossRef] [PubMed]
- Naruphontjirakul, P.; Viravaidya-Pasuwat, K. Development of anti-HER2-targeted doxorubicin–core-shell chitosan nanomolecules for the treatment of human breast cancer. Int. J. Nanomed. 2019, 14, 4105–4121. [CrossRef] [PubMed]
- Naruphontjirakul, P.; Viravaidya-Pasuwat, K. Development of doxorubicin—Core Shell chitosan nanomolecules to treat Cancer. In Proceedings of the 2011 International Conference on Biomedical Engineering and Technology, Kuala Lumpur, Malaysia, 4–5 June 2011.
- Di, H.; Wu, H.; Gao, Y.; Li, W.; Zou, D.; Dong, C. Doxorubicin-and cisplatin-loaded nanostructured lipid carriers for breast cancer combination chemotherapy. Drug Dev. Ind. Pharm. 2016, 42, 2038–2043. [CrossRef] [PubMed]
- Namdari, M.; Cheraghi, M.; Negahdari, B.; Eatemadi, A.; Daraee, H. Recent advances in magnetoliposome for heart drug delivery. Artif. Cells Nanomed. Biotechnol. 2017, 45, 1051–1057. [CrossRef] [PubMed
- Looga, R. Reflex cardiovascular responses to lung inflation: A review. Respir. Physiol. 1997, 12, 95–106. [CrossRef] [PubMed]
- Garcia-Mouton, C.; Hidalgo, A.; Cruz, A.; Pérez Gil, J. The Lord of the Lungs: The essential role of pulmonary surfactant uponinhalation of nanomolecules. Eur. J. Pharm. Biopharm. 2016, 144, 230–243. [CrossRef] [PubMed]
- Jud, C.; Clift, M.; Petri-Fink, A.; Rothen-Rutishauser, B. Nanomaterials and the human lung: What is known and what must bedeciphered to realize their potential advantages? Swiss Med. Wkly. 2013, 143, w13758. [CrossRef] [PubMed]
- Donaldson, K.; Poland, C.A. Inhaled nanomolecules and lung cancer—What we can learn from conventional particle toxicology. Swiss Med. Wkly. 2012, 142, w13547. [CrossRef]
- Kuzmov, A.; Minko, T. Nanotechnology approaches for inhalation treatment of lung diseases. J. Control. Release 2015, 219, 500–518. [CrossRef]
- Azarmi, S.; Roa, W.H.; Löbenberg, R. Targeted delivery of nanomolecules for the treatment of lung diseases. Adv. Drug Deliv. Rev. 2008, 60, 863–875. [CrossRef]
- Han, S.; Liu, Y.; Nie, X.; Xu, Q.; Jiao, F.; Li, W. Efficient Delivery of Antitumor Drug to the Nuclei of Tumor Cells by Amphiphilic Biodegradable Poly(L-Aspartic Acid-co-Lactic Acid)/DPPE Co- Polymer Nanoparticles. Small 2012, 8, 1596–1606. [CrossRef] [PubMed
- Lu, X.; Zhu, T.; Chen, C.; Liu, Y. Right or left: The role of nanomolecules in pulmonary diseases. Int. J. Mol. Sci. 2014, 15, 17577–17600. [CrossRef] [PubMed]
- Aouameur, D.; Cheng, H.; Opoku-Damoah, Y.; Sun, B.; Dong, Q.; Han, Y.; Zhou, J.; Ding, Y. Stimuli-responsive gel-micelles with flexible modulation of drug release for maximized antitumor efficacy. Nano Res. 2018, 11, 4245–4264. [CrossRef]
- Kamat, C.D.; Shmueli, R.B.; Connis, N.; Rudin, C.M.; Green, J.J.; Hann, C.L. Poly( ?-amino ester) Nanoparticle Delivery of TP53 Has Activity against Small Cell Lung Cancer In Vitro and In Vivo. Mol. Cancer Ther. 2013, 12, 405–415. [CrossRef] [PubMed]
- Cordeiro, R.A.; Serra, A.; Coelho, J.F.; Faneca, H. Poly(?-amino ester)-based gene delivery systems: From discovery to therapeuticapplications. J. Control. Release 2019, 310, 155–187. [CrossRef] [PubMed]
- Nan, Y. Lung carcinoma therapy using epidermal growth factor receptor-targeted lipid polymeric nanomolecules co-loaded withcisplatin and doxorubicin. Oncol. Rep. 2019, 42, 2087–2096. [CrossRef]
- Xu, C.; Wang, Y.; Guo, Z.; Chen, J.; Lin, L.; Wu, J. Pulmonary delivery by exploiting doxorubicin and cisplatin co-loadednanomolecules for metastatic lung cancer therapy. J. Control. Release 2019, 295, 153–163. [CrossRef]
- Tan, S.; Wang, G. Redox-responsive and pH-sensitive nanomolecules enhanced stability and anticancer ability of erlotinib to treatlung cancer in vivo. Drug Des. Devel. Ther. 2017, 11, 3519–3529. [CrossRef]
- Wang, X.; Chen, H.; Zeng, X.; Guo, W.; Jin, Y.; Wang, S. Efficient lung cancer- targeted drug delivery via a nanoparticle/MSCsystem. Acta Pharm. Sin. B 2019, 9, 167–176. [CrossRef]
- Rehman, S.; Nabi, B.; Pottoo, F.H.; Baboota, S.; Ali, J. Nanoparticle based gene therapy approach: A pioneering rebellion in themanagement of psychiatric disorders. Curr. Gene Ther. 2020, 20, 164–173. [CrossRef]
- Mahmoudi, S.; Ghorbani, M.; Sabzichi, M.; Ramezani, F.; Hamishehkar, H.; Samadi, N. Targeted hyaluronic acid-based lipid nanoparticle for apigenin delivery to induce Nrf2-dependent apoptosis in lung cancer cells. J. Drug Deliv. Sci. Technol. 2019, 49, 268–276. [CrossRef]
- Chan, M.; Huang, W.; Wang, J.; Liu, R.; Hsiao, M. Next-Generation Cancer-Specific Hybrid Theranostic Nanomaterials: MAGE-A3 NIR Persistent Luminescence Nanoparticles Conjugated to Afatinib for In Situ Suppression of Lung Adenocarcinoma Growth and Metastasis. Adv. Sci. 2020, 7, 1903741. [CrossRef] [PubMed]
- Wang, L.; Jia, E. Ovarian cancer targeted hyaluronic acid-based nanoparticle system for paclitaxel delivery to overcome drug resistance. Drug Deliv. 2016, 23, 1810–1817. [CrossRef] [PubMed]
- Sadighian, S.; Rostamizadeh, K.; Hosseini-Monfared, H.; Hamidi, M. Doxorubicin- conjugated core–shell magnetite nanomolecules as dual-targeting carriers for anticancer drug delivery. Colloids Surf. B Biointerfaces 2014, 117, 406–413. [CrossRef] [PubMed]
- Guo, Z.; Sui, J.; Ma, M.; Hu, J.; Sun, Y.; Yang, L. pH-Responsive charge switchable PEGylated ?-poly-l-lysine polymeric nanomolecules-assisted combination therapy for improving breast cancer treatment. J. Control. Release 2020, 326, 350–364. [CrossRef] [PubMed]
- Chen, S.; Huang, S.; Li, Y.; Zhou, C. Recent advances in epsilon-poly-L-lysine and L- lysine-based dendrimer synthesis, modifica-tion, and biomedical applications. Front. Chem. 2021, 9, 169. [CrossRef]
- Shi, C.; He, Y.; Feng, X.; Fu, D. ?-Polylysine and next-generation dendrigraft poly-L- lysine: Chemistry, activity, and applicationsin biopharmaceuticals. J. Biomater. Sci. Polym. Ed. 2015, 26, 1343–1356. [CrossRef]
- Devi, L.; Gupta, R.; Jain, S.K.; Singh, S.; Kesharwani, P. Synthesis, characterization and in vitro assessment of colloidal gold nanomolecules of Gemcitabine with natural polysaccharides for treatment of breast cancer. J. Drug Deliv. Sci. Technol. 2020, 56, 101–565. [CrossRef]
- Kush, P.; Bajaj, T.; Kaur, M.; Madan, J.; Jain, U.K.; Kumar, P.; Deep, A.; Kim, K.H. Biodistribution and pharmacokinetic study of gemcitabine hydrochloride loaded biocompatible iron-based metal organic framework. J. Inorg. Organomet. Polym. Mater. 2020, 30, 2827–2841. [CrossRef]
- Pooja, D.; Panyaram, S.; Kulhari, H.; Reddy, B.; Rachamalla, S.S.; Sistla, R. Natural polysaccharide functionalized gold nanoparti- cles as biocompatible drug delivery carrier. Int. J. Biol. Macromol. 2015, 80, 48–56. [CrossRef]
- Farid, R.M.; Gaafar, P.M.E.; Hazzah, H.A.; Helmy, M.W.; Abdallah, O.Y. Chemotherapeutic potential of L-carnosine from stimuli-responsive magnetic nanomolecules against breast cancer model. Nanomedicine 2020, 15, 891–911. [CrossRef] [PubMed]
- Li, X.; Li, W.; Wang, M.; Liao, Z. Magnetic nanomolecules for cancer theranostics: Advances and prospects. J. Control. Release 2021, 335, 437–448. [CrossRef] [PubMed]
- White, H.D.; Chew, D.P. Acute myocardial infarction. Lancet 2008, 372, 570–584. [CrossRef] [PubMed]
- Bhat, T.; Teli, S.; Rijal, J.; Bhat, H.; Raza, M.; Khoueiry, G.; Meghani, M.; Akhtar, M. Costantino Neutrophil to lymphocyte ratioand cardiovascular diseases: A review. Expert Rev. Cardiovasc. Ther. 2013, 11, 55–59. [CrossRef]
- Everson-Rose, S.A.; Lewis, T.T. Psychosocial factors and cardiovascular diseases. Annu. Rev. Public Health 2005, 26, 469–500. [CrossRef]
- Andrade, J.; Khairy, P.; Dobrev, D.; Nattel, S. The Clinical Profile and Pathophysiology of Atrial Fibrillation. Circ. Res. 2014, 114, 1453–1468. [CrossRef]
- Tahere, T.; Zohreh, V.; Robabeh, M.; Mehrdad, N. Quality of Nursing Documentations in CCU by Hospital Information System(HIS). IJCCN 2012, 5, 53– 62.
- Muñoz-Aguirre, P.; Flores, M.; Macias, N.; Quezada, A.D.; Denova-Gutiérrez, E.; Salmerón, J. The effect of vitamin D supplemen- tation on serum lipids in postmenopausal women with diabetes: A randomized controlled trial. Clin. Nutr. Edinb. Scotl. 2015, 34, 799–804. [CrossRef]
- Bartels, K.; Karhausen, J.; Clambey, E.T.; Grenz, A.; Eltzschig, H.K. Perioperative organ injury. Anesthesiology 2013, 119, 1474–1489. [CrossRef]
- Fattahi, H.; Laurent, S.; Liu, F.; Arsalani, N.; Elst, L.V.; Muller, R.N. Magnetoliposomes as multimodal contrast agents for molecular imaging and cancer nanotheragnostics. Nanomedicine 2011, 6, 529–544. [CrossRef]
- Soenen, S.J.; Velde, G.V.; Ketkar-Atre, A.; Himmelreich, U.; De Cuyper, M. Magnetoliposomes as magnetic resonance imagingcontrast agents. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2011, 3, 197–211. [CrossRef] [PubMed]
- Banai, S.; Chorny, M.; Gertz, S.D.; Fishbein, I.; Gao, J.; Perez, L. Locally delivered nanoencapsulated tyrphostin (AGL-2043) reduces neointima formation in balloon- injured rat carotid and stented porcine coronary arteries. Biomaterials 2005, 26, 451– 461. [CrossRef] [PubMed]
- McDowell, G.; Slevin, M.; Krupinski, J. Nanotechnology for the treatment of coronary in stent restenosis: A clinical perspective. Vasc. Cell. 2011, 3, 1–5. [CrossRef] [PubMed]
- Chen, J.; Pan, H.; Lanza, G.M.; Wickline, S.A. Perfluorocarbon nanomolecules for physiological and molecular imaging and therapy. Adv. Chronic Kidney Dis. 2013, 20, 466–478. [CrossRef] [PubMed]
- Cheraghi, M.; Negahdari, B.; Daraee, H.; Eatemadi, A. Heart targeted nanoliposomal/nanomolecules drug delivery: An updated review. Biomed. Pharmacother. 2017, 86, 316–323. [CrossRef]
- Yin, X.; Fu, Y.; Yutani, C.; Ikeda, Y.; Enjyoji, K.; Kato, H. HVJ-AVE liposome-mediated Tissue Factor Pathway Inhibitor (TFPI) gene transfer with recombinant TFPI (rTFPI) irrigation attenuates restenosis in atherosclerotic arteries. Int. J. Cardiol. 2009, 135, 245–248. [CrossRef]
- Haeri, A.; Sadeghian, S.; Rabbani, S.; Shirani, S.; Anvari, M.S.; Dadashzadeh, S. Physicochemical characteristics of liposomes are decisive for their antirestenosis efficacy following local delivery. Nanomed 2017, 12, 131–145. [CrossRef]
- Oduk, Y.; Zhu, W.; Kannappan, R.; Zhao, M.; Borovjagin, A.V.; Oparil, S. VEGF nanomolecules repair the heart after myocardial infarction. Am. J. Physiol.-Heart Circ. Physiol. 2018, 314, H278–H284. [CrossRef
- Schwarz, E.R. Evaluation of the effects of intramyocardial injection of DNA expressing vascular endothelial growth factor (VEGF) in a myocardial infarction model in the rat— Angiogenesis and angioma formation. J. Am. Coll. Cardiol. 2000, 35, 1323–1330. [CrossRef]
- Güngör, S.; Kahraman, E. Nanocarriers mediated cutaneous drug delivery. Eur. J. Pharm. Sci. 2021, 158, 105638. [CrossRef]
- Zhou, J.; Zhang, Z.; Joseph, J.; Zhang, X.; Ferdows, B.E.; Patel, D.N.; Chen, W.; Banfi, G.; Molinaro, R.; Cosco, D.; et al. Biomaterials and nanomedicine for bone regeneration: Progress and future prospects. Exploration 2021, 2, 20210011. [CrossRef]
- Hussein-Al-Ali, S.H.; Hussein, M.Z.; Bullo, S.; Arulselvan, P. Chlorambucil- iron oxide nanomolecules as a drug delivery systemfor leukemia cancer cells. Int. J. Nanomed. 2021, 16, 6205. [CrossRef] [PubMed]
- Gonzalez-Valdivieso, J.; Girotti, A.; Schneider, J.; Arias, F.J. Advanced nanomedicine and cancer: Challenges and opportunities inclinical translation. Int. J. Pharm. 2021, 599, 120438. [CrossRef] [PubMed]
- Tewabe, A.; Abate, A.; Tamrie, M.; Seyfu, A.; Siraj, E.A. Targeted drug delivery— From magic bullet to nanomedicine: Principles, challenges, and future perspectives. J. Multidiscip. Healthc. 2021, 14, 1711. [CrossRef]
- Requicha A.A.G., “Nano robots, NEMS and Nano assembly”, Proceedings of the IEEE, 91(11):1922-1933, 2003
- Check, E., “US urged to provide smallpox vaccines for emergency crews. News,” Nature, 417 (6891): 775–776, 2002.
- Earhart, K.C.; Beadle, C.; Miller, L.K.; Press, M.W.; Gary, G.C.; Ledbetter, E.K.; Wallace, M.R. “Outbreak of influenza in highly vaccinated crewof US Navy ship”. Emerge. Infect. Dis., 7(3):463– 465, 2001.
- Hillman, M.R. “Overview: cause and prevention in bio warfare and bioterrorism”. Vaccine, 20 (25- 26):3055– 3067, 2002.
- Cavalcanti, A.; Shirinzadeh, B.; Freitas Jr., R.A.Kratky, L.C. “Medical Nano robot architecture based on Nano bioelectronics”. Recent Pat. Nanotechnology Bentham Science, 1(1):1–10, 2007.
- Oxford, J.S.; Sefton, A.; Jackson, R.; Innes, W.Daniels, R.S.; Johnson, N.P.A.S. “World War I may have allowed the emergence of “Spanish “influenza.” Infect.Dis. 2(2):111–114, 2002.
- Ahuja, S.P.; Myers, J.R. A “survey on wireless grid computing”. J. Supercomputer. 37 (1), 3– 21,2006
- Brindle, J.A. Tactical military communications. IEEE Common. Mag. 30 (1), 62–72, 1992.
- Couvreur, P.; Vauthier, C. “Nanotechnology: intelligent design to treat complex disease”. Pharm.
- Fienberg, S.E.; Shmueli, G. “Statistical issues and challenges associated with rapid detection ofbioterrorist attacks”. Stat. Med., 24 (4), 513–529, 2007
- Geddes, A.M. “The history of smallpox”. Clin. Dermatol. 24 (3), 152–157, 2006
- O’Toole, T.; Ingles by, T.V. Epidemic response scenario: decision making in a time of plague.
- Cowell, G.; Ammon, C.E.; Hen Gartner, N.W.Hyman, J.M. “Transmission dynamics of the great influenza pandemic” of 1918 in Geneva Switzerland: assessing the effects of hypothetical interventions J. Theor. Biol., 241 (2), 193–204, 2006
- Kilter, M.E.; Gavinio, P.; Lavanchy, D. “Influenza and the work of the world health organization”. Vaccine 20, S5–S14, 2002
- Yan, X.; Zou, Y. “Optimal and sub-optimal quarantine and isolation control in SARS epidemics”
- Yamamoto, N. “Method and apparatus for detecting cancer, influenza, or HIV based on. -Nacetyl- galactosaminidase detection”. 5998132USAug 1999
- Webby, R.J.; Webster, R.G. “Are we ready for pandemic influenza?” Science 302 (5650), 1519– 1522, 2009
- Cavalcanti, A.; Shirinzadeh, B.; Fukuda, T.; Ikeda, S. Hardware architecture for Nano robot application in cerebral aneurysm. IEEE-Nano 2007 Int. Conf.Nanotechnol pp. 237–242, Hong Kong, Aug.2007
- Goicoechea, J.; Zamarreño, C.R.; Matias, I.R.; Arregui, F.J. “Minimizing the photo bleaching of self-assembled multilayers for sensor applications.” Sens. Actuator B- Chem., 126 (1), 41–47, 2007.
- Leary, S.P.; Liu, C.Y.; Apuzzo, M.L.I. Toward the emergence of Nano neurosurgery: Part III. Nano medicine: targeted Nano therapy, Nano surgery, and progress toward the realization of Nano neurosurgery. Neurosurgery, 58 (6), 1009–1025.,2006
- Curtis, A.S.G.; Dalby, M.; Gadegaard, N. “Cell signaling arising from Nano topography: implications for nonmedical devices. Nano medicine, 1 (1), 67–72., 2006
- Adamson, P.B.; Conti, J.B.; Smith, A.L.; Abraham, W.T.; Aaron, M.F.; Aranda, J.M.; Baker, J.; Bourge, R.C.; Warner-Stevenson, L.; Sparks, B.“ Reducing events in patients with chronic heart failure (Reduce) study design: continuous hemodynamic monitoring with an implantable defibrillator. Clin. Car diol., 30 (11), 567– 575.,2007
- Ohki, T.; Ouriel, K.; Silveira, P.G.; Katzen, B.; White, R.; Criado, F.; Dietrich, E. “Initial results of wireless pressure sensing for endovascular aneurysm repair: the APEX trial—acute pressure measurement to confirm aneurysm sac exclusion. J. Vasc. Surg. 45(2), 236–242.,2007
- Ramcke, T.; Rosner, W.; Risch, L. Circuit configuration having at least one Nano electronics Component and a method for fabricating the component. 6442042US, Aug 2002.
- Das, S.; Gates, A.J.; Abdu, H.A.; Rose, G.S.;Picconatto, C.A.; Ellenbogen, J.C. “Designs for ultra- tiny,special-purpose Nano electronic circuits”. IEEE Trans. Circuit’s Syst. I-Regul. Pap.54 (11), 2528– 2540.,2002
- Narayan, R.J.; Kumta, P.N.; Sfeir, C.; Lee, D.-H. Olton, D.; Choi, D. Nanostructured ceramics in medical devices: applications and prospects. JOM56 (10), 38–43., 2004
- Hede, S.; Huilgol, N. “Nano: the new nemesis of cancer. J. Cancer Res. Ther.2 (4), 186– 195.1998
- Vaughn, J.R. “Over the horizon: potential impact of emerging trends in information andcommunication technology on disability policy andpractice.” National Council on Disability,
- Murphy, D.; Challacombe, B.; Nedas, T.; Elhage, O.; Althoefer, K.; Seneviratne, L.; Dasgupta,
- Roue, C.C. “Aneurysm liner. 6350270US Feb.200831) McNeil J.S., “Nano robot Pioneer Reveal Status of Simulator, Stem Cell Work,” Nano Biotech News, Vol.2, n. 36, pp. 4-5, September 2004, www.nanorobotdesign.com/article/Nano biotech pdf
- Cavalcanti A., Freitas Jr. R.A., “NanoroboticsControl Design: A CollectiveBehavior Approach forMedicine”, IEEE Transactions on Nanobioscience, Vol. 4, no. 2, pp. 133-140, June2005.
- Casal A., Hogg T., Cavalcanti A., “Nano robots as Cellular Assistants in Inflammatory Responses”, inProc. IEEE BCATS Biomedical Computation at Stanford 2003. Symposium, IEEEComputer Society, Stanford CA, USA, Oct. 2003.
- Katz E., Ricin A., Heleg-Shabtai V., Willner I., Bückmann A.F., “Glucose Oxidase Electrodes via Reconstitution of the Apo-Enzyme: Tailoring of17Novel Glucose Biosensors”, Anal. Chime. Acta.385, 45-58, 1999.
- Mc Devitt M.R., Ma D., Lai L.T., Simon J., BorchardtP., Frank R.K., Wu K., Pellegrini V., Curcio M.J., Miederer M., Bander N.H., Sheinberg D.A. ,“Tumor Therapy with Targeted Atomic Nano generators, “Science 294, 16 November 2001, pp. 1537-1540, Nov. 2001.
- Kumar M.N.V.R., “Nano and Micro particles as Controlled Drug Delivery Devices”, J. PharmacyPharmaceutical Science, 3(2):234-258, 2000.
- Adelman L.M., “On Constructing A Molecular Computer”, DNA Based Computers II: Dimacs Workshop, Jun. 10-12, 1996 (Dimacs Seriesin Discrete Mathematics and Theoretical Computer Science, V. 44), American Mathematical Society, 1996, pp. 1- 21.
- Zhang M., Saharawi C.L., Tao W., Tarn T.J., XiN., LiG., “Interactive DNA Sequence and Structure Design for DNA Nano applications”, IEEE Transactions on Nano bioscience, Vol. 3, No. 4, Dec.2004
- Chatterjee B., Sachdev M., “Design of a 1.7-GHzLow- Power Delay-Fault-Testable 32-b ALU in 180-nm CMOS Technology”, IEEE Transactions on VeryLarge Scale Integration (VLSI) Systems, Vol. 13, no. 11, Nov. 2005.
- Hagiya M., “From Molecular Computing to Molecular Programming”, in Proc.6th DIMACS Workshop on DNA Based Computers, Leiden, the Netherlands, and pp. 198-204. June 2004
- Sun J., GAO M., Feldman J., “Electric Field Directed Layer-by-Layer Assembly of Highly
- Fluorescent CdTe Nanoparticles”, J. of Nanoscience and Nanotechnology, 1(2):133- 136, Jun. 2001.
- Cavalcanti A., Hogg T., Kretly L.C., “Transducers Development for Nanorobotics Applications in Biomedical Engineering”, IEEE NDSIConf. On Nanoscale Devices and System Integration, Houston TX, USA, April 2005.
- Stracke R., Böhm K.J., Burgold J., Schacht H.,UngerE.,“Physicaland Technical Parameters Determining the Functioning of a Kinesin-Based Cell-Free MotorSystem”, Nanotechnology,11(2):52-56, Jun. 2000.
- Reppesgaard L., “Nanobiotechnologie: DieFeinmechaniker der Zukunft nutzen Biomaterial ales biomolecular motors”, Biomedical Microdevices, 2:179-184, 2000.
- Whitcomb L.L., “Underwater Robotics: Out of theResearch Laboratory and into the Field”, pinprick. IEEE Int’l Conf. on Robotics and Automation, a Francisco, CA, USA, pp. 709-716., apr2002
- Cavalcanti A., Hogg T., Shirinzadeh B.,“Nanorobotics System Simulation in 3D Workspaces with Low Reynolds Number”,IEEE-RASMHS Int’lSymposium on Micro-Nanomechatronics and Human Science, Nagoya, Japan, Nov. 2006.
- Braff D., “Fast contact force computation for no penetrating rigid bodies”, in Computer GraphicsProceedings, Annual Conf. Series. ACM SIGGRAPH, pp. 23- 34, 1994.
- Mitch B., Canny J., “Impulse-based simulation of rigid bodies”, Proc. of Symposium on Interactive3DGraphics, pp. 392-398, 1995.
- Wall C., Henrich D., and Wörn H., “Parallel on-line Motion Planning for Industrial Robots,” 3rdASCESpecialty Conf. on Robotics for Challenging Environments, Robotics 98, pp. 308-314, New Mexico, USA, 1998.
- Fukuda T., Arai T., “Prototyping Design and Automation of Micro/Nano Manipulation System,” Proc. of IEEE Int’l Conf. on robotics and Automation (ICRA’00), Vol. 1, pp. 192-197, 2000.
- Fann J.I., Goar F.J.S., Komtebedde J., Oz M.C., Block P.C., Foster P.C., J. Butany, T. Feldman, T.A.Burdon, “Beating Heart Catheter-Based Edgeto-Edge Mitral Valve Procedure in a Porcine Model: Efficacy andHealing Response”, Circulation, 110:988- 993, Aug 2004, circ.ahajournals.org/cgi/content/full/110/8/988
- Stefanie’s C., Toutouzas K., Tsiamis E., StratosC., Vavuranakis M., Kallikazaros I., PanagiotakosD.,Toutouzas P., “Increased Local Temperature in Human Coronary AtheroscleroticPlaques: Anls independent Predictor of Clinical Outcome in Patients Undergoing a Percutaneous Coronary Intervention”, J Am Cull Cardiol,37(5):1277- 1283, Apr. 2001.
- Stefanadis C., Diamantopoulos L., Dernellis J.,Economou E., Tsiamis E., Toutouzas K.,VlachopoulosC., Toutouzas P., “Heat Production ofAtherosclerotic Plaques and Inflammation Assessed by the Acute Phase Proteins in Acute Coronary Syndromes”,J Mol Cell Cardiol, 32(1):43- 52, Jan.2000.
- Ito T., Ikeda U., “Inflammatory cytokines and cardiovascular disease”, Current Drug Targets- Inflammation and Allergy, 2(3):257-265, Sep. 2003.
- Xu C., Wootton D.M., “Platelet Near-Wall Excess in Porcine Whole Blood in Artery- Sized TubesUnder Steady and Pulsatile Flow Conditions”, Bioarcheology41 (2):113- 125, Apr. 2004.
- Cavalcanti, L. Rosen, L. C. Kretly, Moshe. Rosenfeld, Shmuel Einav, “Nanorobotics Challenges in Biomedical Applications, Design and Control”, IEEE ICECS Int’l Conf. on Electronics, Circuits and Systems,Tel-Aviv, Israel, December 2004.
- Cavalcanti A., “Assembly Automation with Evolutionary Nano robots and Sensor- Based Control applied to Nano medicine”, IEEE Transactions on Nanotechnology, Vol. 2, no. 2, pp. 82-87, June 2003
- Cavalcanti A. and Freitas R.A. Jr., “Autonomous multi-robot sensor-based cooperation for Nano medicine,” Int’l J. “Nonlinear Science Numerical Simulation”, Vol. 3, No.4, pp.743-746, August 2002,
- Drexler K.E., “Nano systems: molecular machinery, manufacturing, and computation”, John Wiley &Sons, 1992.
- Fishbine G., “The Investor’s Guide to Nanotechnology & Micro machines”, John Wiley &Sons, 2001.
- Freitas R.A. Jr., “Nano medicine”, Vol. I: Basic Capabilities,” Lands Bioscience, 1999,http://www.nanomedicine.com.
- Geppert L., “The Amazing Vanishing Transistor Act, “Cover story, IEEE Spectrum Magazine, pp. 28-33, October 2002.
- Haiyan M., “From Molecular Computing to Molecular Programming,” Proc. 6th DIMACS Workshop on DNA Based Computers, pp. 198-204, Leiden, Netherlands, 2000.
- Hellman’s A., “German Team Creates New Type of Transistor-Like Device,” News Analysis, IEEE Spectrum Magazine, pp. 20-21, January 2003.
- Kube C.R. and Zhang H., “Task Modelling in Collective Robotics,” Autonomous Robots, 4(1), pp.53-72, 1997.
- Mokhoff N., “Education Overhaul Urged for Nanotech Revolution”, EE Times, Feb. 2003,http://www.theworkcircuit.com/news/OEG20030206S0026.
- Moore S.K., “Just One Word - Plastics,” Special R&D Report, Organic Electronics, IEEE Spectrum Magazine, pp.55-59, September 2002.