Theranogels: Hydrogel-Based System to Be Implemented in Integrated Diagnosis and Targeted Therapy: A Review

Abstract

Theranogels is a type of novel multi-topic drug delivery system which provides combined therapeutic and diagnostic functions [theranostic] within a common hydrogel material. To produce smartgels of theranostic type, stimuli-responsive polymers may be made to be very sensitive to either internal or external stimuli such as pH, temperature,enzymes, magnetic fields, light or redox environment. Theranogels also have unique three-dimensional structural water swollen matrix that can offer high loading capacity, controlled release, compatibility, targeting capacity and sustained release of therapeutics. The past few years have been characterized by the increased interest on theranogels in the treatment of complex pathologies including cancers, central nervous systems diseases, wounded care, inflammatory reactions where conventional drugs have not been able to console due to their low bioavailability, high toxicity and non-specific targeting capabilities. Moreover, theranogels with analysed materials on the basis of nano-particles/contrast media allow the real-time bio-distribution and therapeutic responses analysis in humans. In this review, the types of theranogels, how they are formulated, the types of polymers that are used, how they are assessed, their recent use, their benefits, and shortcomings are all fully described along with future prospects of theranogel based therapies especially in regard to recent advances in translational studies in theranogel therapies done with the incorporation of intelligence-based precision. They are also able to cure gel at the target location without additional solvents, equipments. It enables localised retention of drugs enhancing its efficacy with lower systemic side effects. These Hydrogels are the vectors of controlled and viable drug delivery, primarily applied in cancer treatment, vaccines, wound healing. It facilitates the in-situ gelation under physiological conditions, and facilitates easy and minimally invasive administration.

Keywords

Introduction

They nearly show prerequisite benefits of the application of theranogels in the drug delivery in stimulus-reactive behaviour. They may be designed to react to internal signals like pH, temperature, enzyme and redox state or even external activities like light, magnetic and ultrasound by permitting the release of drugs in controlled and site specific fashion like responsiveness will decrease systemic side effects and will increase therapeutic function. At the same time, the diagnostic features integrated allow Imaging techniques of fluorescence Imaging, MRI, Ultrasound, or photoacoustic imaging^[11].In this respect, theranogels are a personalized medicine strategy since the treatment options can be tailored to clinical feedback in practice, depending on diagnostic results. As an example, the localized delivery of the chemotherapeutic drugs into the cancer site may be achieved with the ability to monitor the cancer regression by use of the image agents. Similarly, it may be applied to the following disorders: neurological, cardiovascular diseases, wound healing and tissue engineering.The other important feature of theranogels is that they could be injected and implanted in a minimal way. Majority of theranogels are sol systems that can be insitu gelated at target site, Thus offering target site specific localization of the theranogel.Recent nanotechnology has given a further improvement in the performance of theranogels by incorporation of gold nanoparticles,magenetic nanoparticles,quantum dots or polymeric nano carriers in the matrics of theranogel which improves the strength,targetability, sensitivity, and the therapeutic efficacy of theranogel.By placing such drugs in theranogels it always provides a strategy of curbing the solubility issues and offers targeted and image guided therapy. The key benefits of these theranogels are that they are easy to administer and their structure is flexible and capable of Safeguarding delicate drugs.Their network structure is porous which enables effective entrapment and release of drugs ^[12].

Theranogels: Idea and Design ^[13,14].

Theranogels is a multifunctional therapeutic and diagnostic/theranostic intelligent hydrogel capable of carrying out therapeutic and diagnostic or theranostic functions simultaneously within a single system.That provides controlled drug delivery as well as real-time imaging or monitoring of the disease. The working concept of theranogels has been outlined to integrate the elements of therapy and the diagnostic by the smart, stimuli-responsive hydrogel systems. The basic principle of about theranogels usage is to entrap therapeutic and diagnostic materials by using their polymeric construction as a three-dimensional structure, which is intelligent to react to biological environments.To begin with theranogels is delivered to the target site as an injectable sol that may self-gel under the influence of the bodily environment such as temperature, pH, entrapping therapeutic and diagnostic materials by the three dimensional polymeric arrangement that are intelligent to react to the biological environment. Continuous release of the therapeutic agent will be done gradually. The release of these drugs was as a result of different processes which included diffusion, polymers swelling. Together, the diagnostics of fluorescent dyes, contrasting agents, magnetic nanoparticles or biosensors will allow real-time disease development and therapeutic effects to be tracked. This agents generates observable signals, Visualization through imaging types such as MRI, fluorescence imaging, ultrasound or photoacoustic imaging.The theranogels also adapts to alteration in disease microenvironment during therapy, e.g. tumor shrinkage or reduction in inflammatory response by regulating drug release and diagnostic reporting.The theranogels essentially entailed a three dimensional, cross-linked hydrogel framework that constituted the structural framework of the framework that incorporated therapeutic,diagnostic -imaging and stimuli-responsive theorists in a solitary framework.The porous structure enabled high absorption of water, biocompatibility, and controlled interaction with bilogical tissues.Polymeric network is the skeleton of the theranogel that gives the gel the desired mechanical stability,elasticity and tissue like properties, loading of drugs, active agent protection, swelling behaviour, degradation rate and controlled release, stimuli responsiveness of the theranogel which includes pH, temperature and enzyme to permit site specific and sustained therapeutic effect. Localized delivery Therapeutic drugs and imaging agents are physically encapsulated or chemically conjugated or embedded within therapeutic nanoparticles into theranogels.Localized release Therapeutic drugs and imaging agents are either delivered by diffusion mechanism of localized delivery or degradation of the gel.

Mechanism of Theranogels ^[15,16,17]

The mechanisms that underlie theranogels are based on the fact that theranogels can incorporate targeted therapy along with real-time diagnosis in a smart hydrogel system. The mechanism can be outlined in the following way:Administration and formation of gels: Theranogels are commonly administered in the form of a sol (liquid) formulation capable of being injected into the body in a liquid state. When introduced into the body, they become a gel at the point of operation and is as a result of the influence of physiological conditions such as temperature, pH, and ion strength.

Localization at Target site: Theranogel remains at the target site, which consists of the diseased tissues, in order to avoid the previous distribution of the therapeutic compounds.Stimuli-Responsive action: The theranogel responds to internal (pH variation,Presence of enzymes, Reductive conditions) or external stimuli (light,Magnetic field,Ultrasound). All of them lead to alterations of the polymer network such as swelling, degradation, bond breaking.Controlled Release of therapeutic agents: The therapeutic agents are delivered in a controlled or sustained form through diffusion, swelling or degradation of hydrogel matrices. This improves the efficacy of drugs and reduces side effects in the body.Diagnostic funactions Simultaneously, diagnostic/contrast agents in the gel generate detectable signals (fluorescence, magnetic resonance imaging, ultrasound, and photoacoustic signals). Drug delivery and disease progress can be monitored in real-time.Feedback and individualised therapy: This allows continual feedbacks of the results of the diagnosis, which will allow modifications and adjustments based on the response of the treatment hence helpful in personalised and precision medicine.Theranogels operate on the concept of the development of a localized stimulus-reactive hydrogel on the target site that may liberate drugs in a controlled manner with concomitant diagnostic signals increases the efficacy of therapies.

Formulation Techniques of Theranogels ^[19,21,21].

Physical Cross-linking process: The methods are based on the gelation mechanism based on non-covalent interactions such as interactions between hydrogen bonds, ionic interactions, or hydrophobic interactions.There is no requirement of chemical cross-linking agents. Applicable in heat-sensitive, pH-sensitive and ion-sensitive. Shelters the biological processes of the drugs and imaging agents.Chemical Cross Linking Process: The cross-linking of polymers is done by the covalent bonds which are formed by the chemical cross-linking reactions or polymerization reactions. Proffers good or excellent gel strength Enables a perfect control of degradation and drug release Applied in long-term therapy sessions.

Examples: Photo-cross-linked theranogels or enzyme-cross-linked theranogels.

In Situ Gelation Technique: Theranogels are administered as a liquid (sol) that solidifies at the target when responding to physiologic stimuli. Minimally invasive offers local drug delivery Applying to wounds healing remedy and cancer treatment.Embedded gel method Nanoparticle: Nanoparticles loaded with a drug or imaging agent are first prepared and dispersed all over the hydrogel base. Enhances loading capacity and image sensitivity of drugs.Self-Assembly method: Self-assembly of amphiphilic polymers or peptides makes up a gel structure. No external cross-linkers required High biocompatibility Biomolecule delivery can be used.Emulsion/Solvents Casting Technique: The polymers and drugs are dissolved in suitable solvents and gelled, mostly with hydrophobic drugs, and in that case. Removal of solvents must be tenacious to facilitate equal distribution of drugs.

Applications of Theranogels ^[22,23,24]

An evolving form of smart biomaterials, theranogels combine diagnostic capabilities and therapeutic delivery within a mono-culture base. Their tunable nature, biocompatibility and stimuli-based functionality allow targeted disease treatment, controlled drug delivery as well as real-time tracking. Theranogels are used in major ways as summarized as follows.

Cancer Theranostics Theranogels: Theranogels have broad applications in oncology in localized drug delivery with tumor imaging Theranogels can be engineered with pH-, redox-, and enzyme-responsive linkage to selectively release chemotherapeutics in the acidic and enzyme-rich tumor microenvironment. At the same time, real-time visualization of the tumor, monitoring of the treatment process, and evaluation of the therapeutic effectiveness have become possible with the help of imaging agents, e.g., fluorescent dyes, quantum dots, or magnetic nanoparticles. In situ forming theranogels that are injected into the body further increase retention of the tumor and reduces systemic toxicity. Targeted Drug Delivery Systems: Site-specific and controlled drug release is enhanced by Theranogels and this offers a better bioavailability and minimizes off-target effects. Small molecules, proteins, peptides and nucleic acids can be encapsulated in their porous network. Theranogels are also very appropriate to chronic and localized diseases because they respond to physiological signals like pH or temperature to release at the affected site on demand. Neurodegenerative and Central Nervous Systems Disorders: On neurological illnesses like Parkinson, Alzheimer, and brain tumors, theranogels have provided localized, protracted medication delivery to the impacted area bypassing the blood-brain barrier. Adding the imaging agents is the capability to trace the drug distribution and disease progression and to tailor therapeutic approaches. Neurotoxicity and inflammation is also reduced by biodegradable theranogels. Wound Healing and Tissue Regeneration: The high water content, biocompatibility and capacity of theranogels to deliver growth factors, antimicrobial agents and anti-inflammatory drugs make them a useful tool in wound management and regenerative medicine. Embedded imaging probes enable real-time wound healing, infection, and tissue regeneration monitoring, which enhances clinical outcomes in diabetic and chronic wounds. Inflammatory and Autoimmune Disease Controlled Release: Theranogels which respond to stimuli are useful in the treatment of inflammatory diseases which include arthritis, inflammatory bowel disease and psoriasis. The pH- and enzyme-responsive gels can release anti-inflammatory drugs selectively to affected tissues and diagnostic elements can be used to visualise the severity of inflammation and therapeutic response so as to optimise dosing.Photodynamic Therapy and Photothermal Therapy Theranogels. Photothermal and photodynamic therapy (PTT/PDT) is based on the use of theranogels containing photo-responsible agents (e.g., gold nanorods or photosensitizers). These gels produce heat or reactive oxygen species on exposure to light and cause the destruction of specific cells. Real-time evaluation of the effectiveness of treatment and light guidance are made possible by the use of concurrent imaging. Imaging-Directed Therapy and Disease Surveillance: Theranogels that contain contrast agents to either MRI, CT or fluorescence imaging allow non-invasive diagnosis of disease and monitoring treatment. Guided Theranogels Imaging Guided Novel Imaging-guided theranogels can assist clinicians to visualize drug release, biodistribution and treatment response to aid precision medicine and personalized therapy. Minimally Invasive Therapies and Injectable Therapies: Injectable theranogels which change sol to gel in vivo are especially useful in the treatment with minimal invasion. They match irregular shapes of tissue, offer long-term local drug retention and lessen the frequency of repetition. The applications of these systems are in cancer treatment, post-operative administration of drugs, and local analgesia. Antimicrobial and Infection Control Applications: Theranogels are also used   as more frequently used in the diagnosis and treatment of infections, in particular biofilm-associated and drug-resistant infections. Antimicrobial agents and imaging probes can be used to detect infection at an early stage and release antimicrobials in a controlled way, preventing the development of resistance and improving treatment. Individualized and Precision Medicine: The theranogels allow customization of therapeutic regimens by incorporating multi-stimuli responsiveness with diagnostic feedback depending on individual disease states of the patient. Such versatility of theranogels as personalized medicine is a scenario in which the theranogels are utilized to customize treatment and diagnostics in real-time with biological response. Theranogels have become flexible platforms which can find application in diverse areas of cancer therapy, targeted drug delivery, regenerative medicine, infection control and personalized healthcare. Their versatility to integrate therapy and diagnostics, as well as stimuli-responsive behavior, make theranogels potentially useful in the next-generation biomedical use and clinical translation.

Personalized and Precision Medicine Using Theranogels ^[25,26,27]

The idea of personalized and precision medicine is to tailor treatment approaches to the genetic profile of a specific patient, disease phenotype, and moving biological reactions. Theranogels are positioned in the unique way to enable this paradigm by combining targeted drug delivery, real-time diagnostics and stimuli-responsive control on a single platform. This two-fold use is useful in enabling clinicians to follow through the treatment regimens and adjust them according to patient-specific responses.Theranogels respond to pathophysiological signals like pH changes, enzyme excessive expression, redox status, and temperature change in diseased tissue. Theranogels can be used to deliver therapeutic payloads to a particular site by selectively responding to these microenvironmental signals, ensuring the release of therapeutic payloads in the target site only. This lessens interpatient differences in drug reaction and enhances treatment outcomes. Drug Dose and Release Kinetics of the Patient: Theranogels have tunable and adjustable release kinetics unlike conventional delivery systems where the release profile is fixed. The polymers can be varied in terms of composition, crosslink density and stimuli sensitivity to change drug dosage, release rate and time. This flexibility facilitates dose individualization that is imperative in disease with narrow therapeutic window like cancer and neurodegenerative disorders. Feedback On Treatment and Real-Time Optimization: Drug distribution and therapeutic response can be monitored continuously by incorporation of diagnostic agents (fluorophores, MRI contrast agents, biosensors) into theranogels. The feedback of real-time imaging enables clinicians to assess the effectiveness of treatment and modify the therapy based on the results, which then turns the non-adaptive treatment regimens into adaptive therapeutic regimens. Biomarker-Driven Therapy: It is possible to design theranogels to react to given biomarkers, including overexpressed enzymes (MMPs in cancer), inflammatory mediators or redox markers. This behavioral response to biomarks can be used to stratify the treatment of patients in that only patients who express specific disease markers are treated to improve efficacy and reduce unnecessary exposure.Combination with Genomic and Molecular Profiling: The development of genomics and proteomics has made it possible to profile patients. Theranogels may be programmed to do individual gene-specific therapies, such as siRNA, miRNA components, and CRISPR, depending on the single genetic mutation. This combination puts theranogel systems in line with genome-directed precision medicine, especially in cancer and rare genetic diseases. The Multi-Mode Therapy Customization: Theranogels are used to permit combination therapies through co-delivery of more than one drug, or as a way of combining chemotherapy with photothermal or immunotherapy. The modalities of treatment can be tailored to the pattern of response of the patient to create a synergetic and sequential therapeutic approach based on the stage and progression of the disease. Less Interpatient Variability and Adverse Effects: The theranogels will be used to reduce interpatient variability and off-target toxicity since they can localize drug action and limit systemic exposure. It is especially useful in the elderly, pediatric, and polymedicated patients, in whom the traditional dosing usually results in adverse drug reactions. Personalized Healthcare through Data: Theranogels are part of data-intensive therapeutic ecosystems in which imaging and sensor data can be compared with electronic health records and AI analytics. These data-driven strategies facilitate predictive analytics, treatment planning, and resultant forecasting and develop precision health systems. Clinical Implications and Future Prognosis: Theranogels in personalized medicine oncology Theranogels in personalized medicine have the potential to be useful in patient-centric therapy, especially in cancer, neurodegenerative diseases, inflammatory conditions, and regenerative medicine. Nonetheless, there are weaknesses including complexity of regulations, scalability, and long-term safety assessment that need to be overcome in order to facilitate a wide clinical implementation. More interdisciplinary research is anticipated to hasten, in the future, the translation of theranogels into precision therapeutics.Artificial Intelligence (AI) finds more applications in designing, optimization, and development of theranogels. This has made it much more efficient in the process. AI also helps to solve the formulation issues and enhance the effectiveness of the theranogel. Design and optimization of polymers: The AI algorithms can predict the most suitable combinations of the polymers and the cross linking density to suit the requirements associated with mechanical properties, swelling behaviour. The machine learning models have the capability to pre-filter the properties of the polymer and then experiments are carried out. AI predicts the interactions between the drug and polymer in order to achieve an optimised loading efficacy. Simulations show the kinetic processes of drug release, and it is optimizing of sustained and targeting release.AI helps in the selection of appropriate nanoparticles in imaging and cancer treatment. Tunes the nanoparticle size, surface modification and distribution in the hydrogel network. Machine learning can also predict the behavior of theranogels when it gets into contact with either pH, temperature, enzymes, or light, which may be used to control the behavior. AI models have the potential to assess the level of biocompatibility and toxicity of any theranogel compositions proposed prior to any live subject test. Reduces the rates of experimental failure and enhances translation potential.

CONCLUSION

The new type of smart biomaterials is referred to as theranogels that have innovative functions in both therapeutic and diagnostics functions in a single platform system. Their regulated drug delivery, stimuli response, imaging, and lack of toxicity are very promising in precision medicine and cancer therapies.Despite various challenges, including stability, drug loading capacity, toxicity of the imaging agent, and regulatory challenges, recent advancement of nanotechnology, AI-assisted design, and hybrid polymers are rapidly advancing towards translation of theranogels into the future. In order to achieve effective, safe and controlled therapeutic uses on personal medicine, theranogels can be significant in the future.

REFERENCES

1. Karthikeyan, L. & Kang, H. W. Recent progress in multifunctional theranostic hydrogels: the cornerstone of next?generation wound care technologies, Biomaterials Science, 2025.
2. Tang, Y. et al., Innovative theranostic hydrogels for targeted gastrointestinal cancer treatment, Journal of Translational Medicine, 2024.
3. Jirvankar, P., Agrawal, S., Chambhare, N., & Agrawal, R., Harnessing Biopolymer Gels for Theranostic Applications, Gels, 2024.
4. Chen, S. et al., Theragenerative injectable bone?adhesive hydrogels for combined photothermal osteosarcoma therapy and bone repair, Biomaterials Science, 2025.
5. Kim, J. I. et al., Long?term theranostic hydrogel system for solid tumors, Biomaterials, 2012.
6. Yan, B. et al., A thermo?sensitive peptide hydrogel loaded with paclitaxel and nanosheets for chemo?photothermal therapy, Frontiers in Pharmacology, 2025.
7. Todkar, S. R. et al., Hydrogel platforms addressing multiple applications in medicinal and drug delivery, Journal of Drug Delivery & Therapeutics, 2025.
8. Peppas, N. A., Slaughter, B. V. & Kanzelberger, M. Hydrogels, in Polymer Science: A Comprehensive Reference, Elsevier, 2012.
9. Zhang Y, Lu Y, Li S, Zheng F, Dong Y, Tang H, et al. Precision theranostics in cervical cancer: Stimuli-responsive hydrogels for targeted therapy and diagnosis. Mater Today Bio. 2025; (review).
10. Siddique MI. Stimuli-responsive hydrogels for controlled drug delivery in oncology: A comprehensive review. Asian J Pharm. 2025.
11. Dreiss, C. A. Hydrogel design strategies for drug delivery, Current Opinion in Colloid & Interface Science, 2020.
12. Cascone, S. & Lamberti, G. Hydrogel?based commercial products for biomedical applications: a review, International Journal of Pharmaceutics, 2020.
13. Bashir, S. et al. Fundamental concepts of hydrogels: Synthesis, properties, and their applications, Polymers, 2020.
14. Nichol, J. W. et al., Cell?laden GelMA hydrogels as modular tissue culture platforms, Biomaterials, 2010.
15. Yue, K. et al., Gelatin methacryloyl (GelMA)?based hydrogels for tissue engineering, Biomaterials, 2015.
16. Loessner, D. et al., Functionalization and preparation of GelMA hydrogels, Nature Protocols, 2016.
17. Rana P, Singh C, Kaushik A, Saleem S, Kumar A. Recent advances in stimuli-responsive tailored nanogels for cancer therapy: From bench to personalized treatment. J Mater Chem B. 2024;12(8):1875–1898.
18. Zhang Y, Li X, Wang Q, Chen J. Theranostic hydrogels: Construction strategies and applications. Chem Eng J. 2025;505:159545.
19. Podgórna K, et al. Theranostic nanogels: multifunctional agents for simultaneous therapeutic delivery and diagnostic imaging. Nanoscale. 2024;16(15):7325–7348.
20. A Review of Nanogels as Novel Drug Delivery Systems. Asian J Pharm Clin Res. 2023;16(4):10-17.
21. A Review on Nanogels. IT Medical Team. 2024; overview of nanogel formulation techniques.
22. Theranostic hydrogels: construction strategies and applications. Chem Eng J. 2025; review.
23. Jirvankar P, Agrawal S, Chambhare N, Agrawal R. Harnessing biopolymer gels for theranostic applications: Imaging agent integration and real-time monitoring of drug delivery. Gels. 2024;10(8):535.
24. Li H, Zhao Y, Wang L. Precision theranostics in cervical cancer: Stimuli-responsive hydrogels for tumor microenvironment-targeted therapy and diagnosis. Biomed Pharmacother. 2025;176:115782.
25. Tang M, Song J, Zhang S, Liu Y, Chen X. Innovative theranostic hydrogels for targeted gastrointestinal cancer treatment. J Transl Med. 2024;22(1):970.
26. Martins JP, Sousa F, Sarmento B. Biologics, theranostics, and personalized medicine in drug delivery systems. Pharmacol Res. 2024;201:107086.
27. Chen D, Liu Y, Zhang L, Wang J. Theranostic nanogels: Multifunctional agents for simultaneous therapeutic delivery and diagnostic imaging. Nanoscale. 2024;16(15):7325–7348.