Application of Hydrogel as Drug Carrier in Tumor Therapy
DOI:
https://doi.org/10.54097/55a06778Keywords:
Hydrogel, Drug Delivery, Tumor Treatment, Stimulus Response, Tumor Microenvironment, Local TreatmentAbstract
Hydrogels, as functional materials possessing both excellent biocompatibility and tunable physicochemical properties, have demonstrated significant application potential in cancer therapeutics. In recent years, with rapid advancements in biomedical engineering technologies, substantial progress has been achieved in hydrogel-based drug delivery systems. This review systematically summarizes the latest research advances in hydrogel carriers for cancer treatment, with particular emphasis on their application advantages in controlled drug release, intelligent tumor microenvironment regulation, and multimodal combination therapy. Studies have revealed that hydrogels, by virtue of their unique physicochemical characteristics including superior biocompatibility, precisely tunable degradation kinetics and drug release profiles, have emerged as a highly promising drug carrier platform in oncology. Notably, stimuli-responsive hydrogels can react to external triggers such as temperature, pH or light irradiation, enabling intelligent drug release and thereby significantly enhancing therapeutic efficacy. With deepening understanding of structure-property relationships and continuous innovation in fabrication technologies, the application prospects of hydrogels in precision cancer therapy are expected to expand further.
Downloads
References
[1] Siegel, R.L., et al., Cancer statistics, 2025. CA Cancer J Clin, 2025. 75(1): p. 10-45.
[2] Yao, J., et al., Biomaterials enhancing localized cancer therapy activated anti-tumor immunity: a review. J Mater Chem B, 2024. 13(1): p. 117-136.
[3] Hamley,I.W.,Self-Assembly,Bioactivity,and Nanomaterials Applications of Peptide Conjugates with Bulky Aromatic Terminal Groups. ACS Appl Bio Mater, 2023. 6(2): p. 384-409.
[4] Kobrin, R.L.,et al.,Chitosan-Glycerol Injectable Hydrogel for Intratumoral Delivery of Macromolecules. Gels, 2025. 11(8).
[5] Wang, Z.,et al., Recent advances of injectable in situ-forming hydrogels for preventing postoperative tumor recurrence. Drug Deliv, 2024. 31(1): p. 2400476.
[6] Skopinska-Wisniewska,J.,S.De la Flor, and J. Kozlowska, From Supramolecular Hydrogels to Multifunctional Carriers for Biologically Active Substances. Int J Mol Sci, 2021. 22(14).
[7] Bal, T., B. Kepsutlu, and S. Kizilel, Characterization of protein release from poly(ethylene glycol) hydrogels with crosslink density gradients. J Biomed Mater Res A, 2014. 102(2): p. 487-95.
[8] Roca-Arroyo, A.F., et al., Hydrogel Network Architecture Design Space: Impact on Mechanical and Viscoelastic Properties. Gels, 2025. 11(8).
[9] Jiang, Y., et al., Natural Polymer-based Stimuli-responsive Hydrogels. Curr Med Chem, 2020. 27(16): p. 2631-2657.
[10] Bittner, S.M., et al., Swelling Behaviors of 3D Printed Hydrogel and Hydrogel-Microcarrier Composite Scaffolds. Tissue Eng Part A, 2021. 27(11-12): p. 665-678.
[11] Seo, H.S., et al., Short Review on Advances in Hydrogel-Based Drug Delivery Strategies for Cancer Immunotherapy. Tissue Eng Regen Med, 2022. 19(2): p. 263-280.
[12] Xu,F.,et al.,Hydrogels for Tissue Engineering: Addressing Key Design Needs Toward Clinical Translation. Front Bioeng Biotechnol, 2022. 10: p. 849831.
[13] Wang,J.,et al., An injectable PEG hydrogel controlling neurotrophin-3 release by affinity peptides. J Control Release, 2021. 330: p. 575-586.
[14] Zheng,B.D.and M.T. Xiao, Polysaccharide-based hydrogel with photothermal effect for accelerating wound healing. Carbohydr Polym, 2023. 299: p. 120228.
[15] Zhou,S.,et al., An Immune-Regulating Polysaccharide Hybrid Hydrogel with Mild Photothermal Effect and Anti-Inflammatory for Accelerating Infected Wound Healing. Adv Healthc Mater, 2024. 13(20): p. e2400003.
[16] Kim, M.H.,et al.,Dual Functionalization of Gelatin for Orthogonal and Dynamic Hydrogel Cross-Linking. ACS Biomater Sci Eng, 2021. 7(9): p. 4196-4208.
[17] Shatabayeva,E.O.,et al.,Enhancing Mucoadhesive Properties of Gelatin through Chemical Modification with Unsaturated Anhydrides. Biomacromolecules, 2024. 25(3): p. 1612-1628.
[18] Panjaitan,F.C.A.,et al.,Bioactive Properties of Enzymatic Gelatin Hydrolysates Based on In Silico, In Vitro, and In Vivo Studies. Molecules, 2024. 29(18).
[19] Haq,M.A.,Y. Su, and D. Wang, Mechanical properties of PNIPAM based hydrogels: A review. Mater Sci Eng C Mater Biol Appl, 2017. 70(Pt 1): p. 842-855.
[20] Cohen,E. and E. Poverenov, Hydrophilic Chitosan Derivatives: Synthesis and Applications. Chemistry, 2022. 28(67): p. e202202156.
[21] Bayer, I.S., Hyaluronic Acid and Controlled Release: A Review. Molecules, 2020. 25(11)
[22] Imran, H.,et al.,Optimized DOX Drug Deliveries via Chitosan-Mediated Nanoparticles and Stimuli Responses in Cancer Chemotherapy: A Review. Molecules, 2023. 29(1).
[23] Gagneja,S., N. Capalash, and P. Sharma, Hyaluronic acid as a tumor progression agent and a potential chemotherapeutic biomolecule against cancer: A review on its dual role. Int J Biol Macromol, 2024. 275(Pt 2): p. 133744.
[24] Shiraishi,K. and M. Yokoyama, Antigenicity Extension: A Novel Concept Explained by the Immunogenicity of PEG. ACS Bio Med Chem Au, 2025. 5(1): p. 42-54.
[25] Wang, Y.,et al., Size Control and Enhanced Stability of Silver Nanoparticles by Cyclic Poly(ethylene glycol). Polymers (Basel), 2022. 14(21).
[26] Brás, A.,et al., Chain-End Effects on Supramolecular Poly(ethylene glycol) Polymers. Polymers (Basel), 2021. 13(14).
[27] Habib,M.,et al.,Dual Cross-Linked Stimuli-Responsive Alginate-Based Hydrogels. Biomacromolecules, 2024. 25(3): p. 1660-1670
[28] Zhao, Z., et al., Crosslinked Biodegradable Hybrid Hydrogels Based on Poly(ethylene glycol) and Gelatin for Drug Controlled Release. Molecules, 2024. 29(20).
[29] Carpentier, N., et al., Gelatin-Based Hybrid Hydrogel Scaffolds: Toward Physicochemical Liver Mimicry. Biomacromolecules, 2023. 24(10): p. 4333-4347.
[30] Mohanty, S., et al., Exploring the potential of polysaccharide-based hybrid hydrogel systems for their biomedical and therapeutic applications: A review. Int J Biol Macromol, 2024. 256(Pt 1): p. 128348.
[31] Gao, Y., K. Peng, and S. Mitragotri, Covalently Crosslinked Hydrogels via Step-Growth Reactions: Crosslinking Chemistries, Polymers, and Clinical Impact. Adv Mater, 2021. 33(25): p. e2006362.
[32] Das, S. and D. Das, Rational Design of Peptide-based Smart Hydrogels for Therapeutic Applications. Front Chem, 2021. 9: p. 770102.
[33] Muir, V.G. and J.A. Burdick, Chemically Modified Biopolymers for the Formation of Biomedical Hydrogels. Chem Rev, 2021. 121(18): p. 10908-10949.
[34] Pramanik, B., Short Peptide-Based Smart Thixotropic Hydrogels. Gels, 2022. 8(9).
[35] Shan, J., et al., TEMPO/TCC as a Chemo Selective Alternative for the Oxidation of Hyaluronic Acid. Molecules, 2021. 26(19).
[36] Han, C., et al., Dual-crosslinked hyaluronan hydrogels with rapid gelation and high injectability for stem cell protection. Sci Rep, 2020. 10(1): p. 14997.
[37] Miao, Y., et al., Evaluation of living bacterial therapy assisted by pH/reactive oxygen species dual-responsive sodium alginate-based hydrogel for wound infections. Int J Biol Macromol, 2024. 271(Pt 2): p. 132536.
[38] Deng, L., et al., Double Cross-Linked Chitosan/Bacterial Cellulose Dressing with Self-Healable Ability. Gels, 2023. 9(10).
[39] Han, Y., Y. Cao, and H. Lei, Dynamic Covalent Hydrogels: Strong yet Dynamic. Gels, 2022. 8(9).
[40] Sujan, M.I., et al., Bi-functional silica nanoparticles for simultaneous enhancement of mechanical strength and swelling capacity of hydrogels. RSC Adv, 2020. 10(11): p. 6213-6222.
[41] Cadamuro, F., et al., Alginate-Gelatin Self-Healing Hydrogel Produced via Static-Dynamic Crosslinking. Molecules, 2023. 28(6).
[42] Hoque, J., N. Sangaj, and S. Varghese, Stimuli-Responsive Supramolecular Hydrogels and Their Applications in Regenerative Medicine. Macromol Biosci, 2019. 19(1): p. e1800259.
[43] Wang, Q., et al., Nano-crosslinked dynamic hydrogels for biomedical applications. Mater Today Bio, 2023. 20: p. 100640.
[44] Augustin, R. C., G.M. Delgoffe, and Y.G. Najjar, Characteristics of the Tumor Microenvironment That Influence Immune Cell Functions: Hypoxia, Oxidative Stress, Metabolic Alterations. Cancers (Basel), 2020. 12(12).
[45] Xiao, Y. and D. Yu, Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther, 2021. 221: p. 107753.
[46] Jin, M.Z. and W.L. Jin, The updated landscape of tumor microenvironment and drug repurposing. Signal Transduct Target Ther, 2020. 5(1): p. 166.
[47] Bader, J.E., K. Voss, and J.C. Rathmell, Targeting Metabolism to Improve the Tumor Microenvironment for Cancer Immunotherapy. Mol Cell, 2020. 78(6): p. 1019-1033.
[48] Ghalehkhondabi, V., A. Fazlali, and M. Soleymani, Temperature and pH-responsive PNIPAM@PAA Nanospheres with a Core-Shell Structure for Controlled Release of Doxorubicin in Breast Cancer Treatment. J Pharm Sci, 2023. 112(7): p. 1957-1966.
[49] Noddeland, H.K., et al., Design and characterization of matrix metalloproteinase-responsive hydrogels for the treatment of inflammatory skin diseases. Acta Biomater, 2023. 157: p. 149-161.
[50] Balestri, A., et al., PNIPAM-stabilized cubosomes as fusogenic delivery nanovectors for anticancer applications. Colloids Surf B Biointerfaces, 2023. 231: p. 113532.
[51] Xian, S. and M.J. Webber, Temperature-responsive supramolecular hydrogels. J Mater Chem B, 2020. 8(40): p. 9197-9211.
[52] Liu, Z., et al., A Light-Responsive Injectable Hydrogel with Remodeling Tumor Microenvironment for Light-Activated Chemodynamic Therapy. Macromol Biosci, 2023. 23(1): p. e2200329.
[53] Zhai, S., et al., Near-infrared light-responsive on-demand puerarin-releasing injectable hydrogel for promoting healing of infected wounds. Mater Today Bio, 2025. 32: p. 101817.
[54] Xing, Y., B. Zeng, and W. Yang, Light responsive hydrogels for controlled drug delivery. Front Bioeng Biotechnol, 2022. 10: p. 1075670.
[55] Cerdan, K., et al., Magnetic Self-Healing Composites: Synthesis and Applications. Molecules, 2022. 27(12).
[56] Wychowaniec, J.K. and D.F. Brougham, Emerging Magnetic Fabrication Technologies Provide Controllable Hierarchically-Structured Biomaterials and Stimulus Response for Biomedical Applications. Adv Sci (Weinh), 2022. 9(34): p. e2202278.
[57] Kasiński, A., et al., Dual-Stimuli-Sensitive Smart Hydrogels Containing Magnetic Nanoparticles as Antitumor Local Drug Delivery Systems-Synthesis and Characterization. Int J Mol Sci, 2023. 24(8).
[58] Chen, Y., et al., Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery. Bioact Mater, 2025. 53: p. 591-629.
[59] Aram, E., et al., Smart and Multi-Functional Magnetic Nanoparticles for Cancer Treatment Applications: Clinical Challenges and Future Prospects. Nanomaterials (Basel), 2022. 12(20).
[60] Graham, W., et al., Magnetic Nanoparticles and Drug Delivery Systems for Anti-Cancer Applications: A Review. Nanomaterials (Basel), 2025. 15(4).
[61] Mañas-Torres, M.C., et al., Injectable Magnetic-Responsive Short-Peptide Supramolecular Hydrogels: Ex Vivo and In Vivo Evaluation. ACS Appl Mater Interfaces, 2021. 13(42): p. 49692-49704.
[62] Tiwari, O.S., S. Rencus-Lazar, and E. Gazit, Peptide- and Metabolite-Based Hydrogels: Minimalistic Approach for the Identification and Characterization of Gelating Building Blocks. Int J Mol Sci, 2023. 24(12).
[63] Ren, C., et al., Carrier-Free Supramolecular Hydrogel Composed of Dual Drugs for Conquering Drug Resistance. ACS Appl Mater Interfaces, 2019. 11(37): p. 33706-33715.
[64] Chen, L.H., et al., Supramolecular hydrogel for programmable delivery of therapeutics to cancer multidrug resistance. Biomater Adv, 2023. 146: p. 213282.
[65] Garg, A., et al., In-situ gel: A smart carrier for drug delivery. Int J Pharm, 2024. 652: p. 123819.
[66] Kulkarni, N., et al., Emerging Role of Injectable Dipeptide Hydrogels in Biomedical Applications. ACS Omega, 2023. 8(4): p. 3551-3570.
[67] Choi, S.J., et al., Development of injectable colloidal solution forming an in situ hydrogel for tumor ablation. Biomater Sci, 2024. 12(17): p. 4483-4492.
[68] Coulter, S.M., et al., In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System. J Am Chem Soc, 2024. 146 (31): p. 21401-21416.
[69] Liu, C., et al., Application of injectable hydrogels in cancer immunotherapy. Front Bioeng Biotechnol, 2023. 11: p. 1121887.
[70] Zhang, X., et al., Locally Injectable Hydrogels for Tumor Immunotherapy. Gels, 2021. 7(4).
[71] Zang, C., et al., Hydrogel-based platforms for site-specific doxorubicin release in cancer therapy. J Transl Med, 2024. 22(1): p. 879.
[72] Wang, F., et al., Self-assembling paclitaxel-mediated stimulation of tumor-associated macrophages for postoperative treatment of glioblastoma. Proc Natl Acad Sci U S A, 2023. 120(18): p. e2204621120.
[73] Lu, L., et al., The Formation Mechanism of Hydrogels. Curr Stem Cell Res Ther, 2018. 13(7): p. 490-496.
[74] Ahmadi, M., T. Madrakian, and S. Ghavami, Preparation and Characterization of Simvastatin Nanocapsules: Encapsulation of Hydrophobic Drugs in Calcium Alginate. Methods Mol Biol, 2020. 2125: p. 47-56.
[75] Cauwenbergh, T., S. Ballet, and C. Martin, Peptide hydrogel-drug conjugates for tailored disease treatment. Mater Today Bio, 2025. 31: p. 101423.
[76] Zhang,B.,et al., Hydrophilic-Hydrophobic Network Hydrogels Achieving Optimal Strength and Hysteresis Balance. ACS Appl Mater Interfaces, 2024. 16(42): p. 57769-57777.
[77] Bardajee,G.R.,R. Ghadimkhani, and F. Jafarpour, A biocompatible double network hydrogel based on poly (acrylic acid) grafted onto sodium alginate for doxorubicin hydrochloride anticancer drug release. Int J Biol Macromol, 2024. 260(Pt 2): p. 128871.
[78] Davoodi,P.,et al., Drug delivery systems for programmed and on-demand release. Adv Drug Deliv Rev, 2018. 132: p. 104-138.
[79] Roy,A.,et al., pH-Responsive Copolymeric Network Gel Using Methacrylated β-Cyclodextrin for Controlled Codelivery of Hydrophilic and Hydrophobic Drugs. ACS Appl Bio Mater, 2022. 5(7): p. 3530-3543.
[80] Wang,T.,et al., Injectable, Adhesive Albumin Nanoparticle-Incorporated Hydrogel for Sustained Localized Drug Delivery and Efficient Tumor Treatment. ACS Appl Mater Interfaces, 2024. 16(8): p. 9868-9879.
[81] Falcone, N., et al., Peptide Hydrogels as Immunomaterials and Their Use in Cancer Immunotherapy Delivery. Adv Healthc Mater, 2023. 12(27): p. e2301096.
[82] Zhu, X. and S. Li, Nanomaterials in tumor immunotherapy: new strategies and challenges. Mol Cancer, 2023. 22(1): p. 94.
[83] Cao, H., et al., Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity. Signal Transduct Target Ther, 2021. 6(1): p. 426.
[84] Chang, H., et al., Advances in hybrid hydrogel design for biomedical applications: innovations in drug delivery and tissue engineering for gynecological cancers. Cell Biol Toxicol, 2025. 41(1): p. 115.
[85] Dang, W., et al., 3D printed hydrogel scaffolds combining glutathione depletion-induced ferroptosis and photothermia-augmented chemodynamic therapy for efficiently inhibiting postoperative tumor recurrence. J Nanobiotechnology, 2022. 20(1): p. 266.
[86] Wang, M., et al., Enhanced Chemo-Immunotherapy Strategy Utilizing Injectable Thermosensitive Hydrogel for The Treatment of Diffuse Peritoneal Metastasis in Advanced Colorectal Cancer. Adv Sci (Weinh), 2023. 10(35): p. E 2303819.
[87] Liu, W.S., et al., Multifunctional hydrogels based on photothermal therapy: A prospective platform for the postoperative management of melanoma. J Control Release, 2024. 371: p. 406-428.
[88] Chang, R., et al., PMN-incorporated multifunctional chitosan hydrogel for postoperative synergistic photothermal melanoma therapy and skin regeneration. Int J Biol Macromol, 2023. 253(Pt 4): p. 126854.
[89] Zhuang, B., et al., Chemo-photothermal immunotherapy for eradication of orthotopic tumors and inhibition of metastasis by intratumoral injection of polydopamine versatile hydrogels. Acta Pharm Sin B, 2022. 12(3): p. 1447-1459.
[90] Zhang, Q., et al., MMP-2 Responsive Peptide Hydrogel-Based Nanoplatform for Multimodal Tumor Therapy. Int J Nanomedicine, 2024. 19: p. 53-71.
[91] Wang, S., et al., Near-infrared light-controllable MXene hydrogel for tunable on-demand release of therapeutic proteins. Acta Biomater, 2021. 130: p. 138-148.
[92] Zhang, H., et al., Intrinsic PD-L1 Degradation Induced by a Novel Self-Assembling Hexapeptide for Enhanced Cancer Immunotherapy. Adv Sci (Weinh), 2025. 12(2): p. e2410145.
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
