Nanoparticle Based Drug Delivery for Cancer Therapy

Drug delivery systems (DDS) have been used in both clinical and pre-clinical settings to deliver therapeutic substances for treating diseases [1]. Traditional DDS methods involve either oral intake or injection. While conventional DDS methods are easy to administer and generally accepted by patients, they have several significant limitations:

• Limited effectiveness: Many drugs have unpredictable absorption rates when taken by mouth, and the acidic environment in the stomach along with digestive enzymes can break down some drugs before they reach the bloodstream.
• Lack of selectivity: Many drugs have unpredictable absorption rates when taken by mouth, and the acidic environment in the stomach along with digestive enzymes can break down some drugs before they reach the bloodstream.

Controlled drug delivery systems can address several issues that traditional methods struggle with. For example, chemotherapy drugs used to treat cancer are usually spread throughout the body in a non-targeted way, which can damage both healthy and cancer cells. This leads to lower treatment effectiveness and more side effects [2]. Controlled DDSs could be great for delivering chemotherapy drugs, as they can direct the medication specifically to the tumor. This increases the amount of drug reaching cancer cells while reducing harm to normal cells [3, 4]. In addition, controlled DDSs help protect drugs from breaking down or being removed by the body. This is especially useful for delivering proteins and new treatments like gene therapy and RNA interference. They can also help DNA and siRNA avoid being taken up by the reticuloendothelial system or other tissues, as well as prevent them from being broken down by enzymes [5].

Nanoparticle-based drug delivery systems offer a promising way to treat cancer by making treatments more effective and less harmful. These systems use nanoparticles, which are very small particles, usually between 1 and 1000 nanometers in size, to carry drugs directly to cancer cells. This helps reduce damage to healthy tissues and makes the treatment more targeted, which can lead to fewer side effects and better results.

Cancer is a general term that refers to a group of diseases where cells grow out of control and spread uncontrollably.

For many years, scientists have been trying to find out what causes cancer. Some cancers are linked to environmental factors like radiation and pollution. However, lifestyle choices such as eating an unhealthy diet, using tobacco, smoking, experiencing high levels of stress, and not exercising enough also play a big role in increasing cancer risk. While these external factors are well known, it's more difficult to measure how much genetic changes, like mutations in proto-oncogenes, tumor suppressor genes, and genes involved in DNA repair, contribute to cancer development. In fact, only 5 to 10% of cancer cases are connected to inherited genetic factors.

Different types of nanoparticles are utilized in the treatment of cancer (Fig. 1). Nanoparticles have the capability to transport chemotherapy drugs directly to cancer cells, thereby increasing therapeutic effectiveness and reducing side effects. They can also generate heat to destroy cancer cells through a process called hyperthermia. Additionally, nanoparticles can enhance medical imaging techniques, allowing for improved tumor monitoring and precise localization. Overall, nanoparticles present significant potential for improving patient outcomes and advancing the field of oncology [6]. Therefore, it is essential to conduct thorough research on these factors and understand their impact on nanoparticle behavior before progressing to human trials. Furthermore, developing strategies to improve nanoparticle stability and minimize their accumulation in healthy organs will be crucial for their successful application in clinical settings [7]. In this review, we describe the non-drug delivery aspects of cancer therapy.

Fig.1.Different types of nanoparticles are used in cancer treatment

Nanoparticles: -

Nanoparticles (NPs) are particles that are smaller than 100 nm in at least one dimension and have special properties that are not found in larger forms of the same material [8]. They can be grouped into different types based on their shape, such as 0D, 1D, 2D, or 3D [19]. The structure of nanoparticles includes several parts: the surface layer, the shell, and the core, which is the central part and is often considered the main body of the nanoparticle [9]. Because of their unique characteristics, such as a high surface-to-volume ratio, distinct properties, small size, and improved targeting ability, these materials are widely used in many different fields.

Nanoparticles are able to penetrate deep into tissues, which helps improve the enhanced permeability and retention effect. Also, the features on their surface influence how well they are absorbed by the body and how long they stay active by helping them pass through small openings in cell layers. For instance, nanoparticles covered with polyethylene glycol, a water-loving material, are less likely to be detected and removed by the immune system.[10] Moreover, by changing the properties of the material used in nanoparticles, it's possible to control how quickly drugs or active substances are released [11]. Overall, the unique qualities of nanoparticles play a key role in how effectively they work for treating cancer.

Types of Nanoparticles used in Drug Delivery:

1. Inorganic nanoparticles

Inorganic nanoparticles, such as gold and silver nanoparticles, have demonstrated significant potential in cancer treatment due to their distinctive properties. These nanoparticles can be engineered to specifically target cancer cells, thereby increasing the effectiveness of conventional treatments like chemotherapy or radiation therapy. However, there is a need for extensive research to optimize their safety and efficacy. Understanding the long-term effects of nanoparticles on the human body is vital to prevent any unintended harm to patients [12]. Researchers must also tackle the challenge of scaling up nanoparticle production to meet clinical demands. Standardized and cost-effective manufacturing processes are essential for the widespread availability and affordability of these promising cancer treatment options. Moreover, researchers should consider the ethical implications of using nanoparticles in cancer treatment. It is crucial to ensure that the benefits outweigh any potential risks and that patients are fully informed about the use of these innovative therapies [13]. A clinical trial found that nanoparticles combined with chemotherapy drugs enhanced treatment effectiveness by targeting cancer cells while minimizing damage to healthy cells. This breakthrough underscored the importance of understanding how nanoparticles interact with other medications and paved the way for personalized cancer treatment plans tailored to individual patients. Innovative manufacturing techniques, such as continuous flow reactors, have been developed to reduce costs and ensure widespread access to this cutting-edge technology [14]. However, the limited effectiveness of nanoparticle-based cancer treatments for certain types of tumors remains a significant challenge. For example, in pancreatic cancer, dense stromal tissue surrounding the tumor hinders drug penetration, limiting the effectiveness of nanoparticles in certain tumor microenvironments. This challenge has prompted researchers to explore alternative strategies, such as combining nanoparticle-based treatments with other therapeutic approaches like immunotherapy or targeted drug delivery systems [15]. By synergistically leveraging multiple treatment modalities, scientists aim to overcome the limitations posed by dense stromal tissue and enhance the efficacy of cancer treatments in challenging tumor microenvironments.

2. Organic nanoparticles

Organic nanoparticles are a good alternative to metal nanoparticles in medical uses because they are safe for the body and can be made to have special features, like delivering medicine to certain areas or acting as a tool to see inside the body [16]. These nanoparticles have shown promise in treating cancer, as they can target drugs directly to cancer cells, providing a steady and effective treatment [17]. However, organic nanoparticles can also give off light signals when they come into contact with certain body parts, which helps in seeing those areas better. But this method can also cause unwanted side effects and harm, and it's sometimes hard to clearly see the exact areas being treated. More research is needed to fully understand the long-term impacts and risks of using organic nanoparticles in medical treatments [18]. Also, there are worries about these nanoparticles building up in the body over time, which could lead to harmful effects. Therefore, it is very important to do thorough studies to check the safety and effectiveness of organic nanoparticles before they are used widely in medical treatments [19].

3. Hybrid nanoparticles

Hybrid nanoparticles offer a promising solution to issues related to the buildup of organic nanoparticles by combining the benefits of both organic and inorganic materials. By adding inorganic elements such as metals or metal oxides, these nanoparticles can improve their ability to work safely inside the body and lower the chance of being stored in the body over time [20]. Despite this, more research is needed to fully understand how these hybrid nanoparticles interact with the body and what long-term effects they might have. The way the immune system responds to hybrid nanoparticles can depend on their size, shape, and how their surface looks [12]. Although organic nanoparticles are usually considered safe, adding inorganic parts might cause the immune system to react, which could lead to inflammation or other problems. Therefore, it's important to study how the immune system reacts to hybrid nanoparticles and check their safety before using them in medical treatments [21]. A study on hybrid nanoparticles found that smaller ones with a round shape and smooth surface were more likely to pass through the immune system and be seen as safe [16]. However, larger nanoparticles with odd shapes and rough surfaces caused a stronger immune reaction, leading to inflammation and possible health issues. This shows the need to carefully examine the physical features of nanoparticles to ensure they are safe for medical use. For example, gold nanoparticles have been found to trigger immune responses and cause inflammation, indicating that size and shape alone do not always determine safety [22]. Also, some inorganic nanoparticles with irregular shapes and rough surfaces have shown low immunogenicity, which goes against the idea that these features always lead to a strong immune reaction. Thus, having a full understanding of how nanoparticles behave is essential for accurately assessing their safety in medical applications [23].

Targeted nanoparticle drug delivery

Nanoparticle systems covered with pH-sensitive polymers can help solve problems in cancer treatment by delivering medicine straight to the tumor, making the treatment more effective and less harmful to healthy tissues [24]. Better nanoparticle systems that are more sensitive to pH changes can release drugs more accurately and in a controlled way, which overcomes the limits of today's pH-sensitive polymers. A promising method is using nanogels, which are three-dimensional networks made of linked polymers that can hold drugs and react to pH changes. These nanogels can be made to release medicine based on pH levels, allowing the drug to target the tumor site specifically [25].

Fig.2.Nanoparticle-mediated targeted drug delivery to cancer cells

Fig.3.Passive Targeting of Nanoparticles to cancer cells.

Researchers are also investigating stimulus-responsive nanoparticles that can react to various factors, such as temperature or enzymatic activity, to enhance the precision of drug release. These developments have significant potential to transform cancer treatment and improve patient results. pH-responsive nanogels, for example, can be loaded with chemotherapy drugs and injected into the bloodstream, delivering the treatment directly to cancer cells while reducing harm to healthy tissues. This targeted drug delivery method boosts treatment effectiveness and lowers the side effects commonly associated with chemotherapy [26]. However, cancer cells can develop resistance to the effects of nanogels. To address this, combination therapy where multiple drugs are used together to counteract resistance has demonstrated promising outcomes in enhancing chemotherapy efficacy. Researchers are also exploring alternative approaches, such as immunotherapy and gene therapy, to tackle drug resistance and improve treatment outcomes [27]. Additionally, nanotechnology continues to evolve, with ongoing studies aimed at creating more efficient and targeted drug delivery systems capable of overcoming resistance mechanisms and further improving patient care [28].

Based Drug Delivery Systems: -

Nanoparticle-based drug delivery systems have shown promise in making cancer treatment more effective by delivering drugs directly to cancer cells, which helps protect healthy tissues from damage [29]. However, drug resistance is still a big problem that needs to be solved to make the most out of these systems. Scientists are working on ways to beat drug resistance and make these systems work better. One approach is using combination therapies, where multiple drugs are delivered at the same time through nanoparticles. This target different ways cancer cells become resistant to drugs [30]. Nanoparticles can also help drugs get past the defenses that cancer cells use to resist treatment, allowing the drugs to reach their target and work properly. These particles can be designed to release drugs slowly, keeping drug levels steady and reducing side effects. Additionally, researchers are trying to make nanoparticles more precise so they can target cancer cells more accurately while leaving healthy tissue untouched. This could lead to better, more personalized cancer treatments in the future [31]. Gene therapy agents that reverse or inhibit cancer cell drug resistance are under investigation. Nanoparticles can encapsulate chemotherapy drugs and specifically target cancer cells while bypassing the resistance mechanisms that typically make them ineffective. This targeted delivery helps reduce confusion and frustration in patients and increases the effectiveness of treatment. However, not all cancer cells respond equally to nanoparticle-based treatments, as certain mutations or genetic variations may reduce their susceptibility. Some cancer cells may actively expel or neutralize nanoparticles, making them less effective in delivering drugs to their intended targets [32]. Additionally, interactions between nanoparticles and cancer cells can lead to unexpected side effects or toxicities, which could harm healthy tissues and organs. It is important to recognize that the effectiveness of nanoparticle-based treatments can vary depending on the specific type of cancer cells being targeted [33]. Certain cancer cells may possess unique characteristics that make them more resistant to nanoparticle therapies. The delivery method of nanoparticles to cancer cells is also a critical factor. The ability of nanoparticles to efficiently reach and penetrate the tumor site significantly influences their effectiveness [34]. Moreover, understanding the potential long-term effects and safety profile of nanoparticle-based treatments is essential to ensure patient well-being and minimize any unforeseen risks [35].

How Nanoparticles Work in Cancer Drug Delivery: -

Fig.4.Polymeric Nanoparticles