Hydrogels for Cancer Immunotherapy: Strategies From Construction to Application

Abstract

Cancer is a complex disease characterized by systemic dysfunction, necessitating a balance between therapeutic efficacy and safety. Immunotherapy is a core treatment approach for activating the antitumor immune response in the human body. The development of intelligent hydrogels has provided an innovative platform for tumor immunotherapy, owing to their adjustable properties for controlled drug delivery and immune modulation. Tumor immunotherapy has achieved remarkable success in recent years. However, it continues to face critical challenges such as targeting and delivery barriers, suppression by the TME, and immune evasion and drug resistance. In response, as injectable or implantable biomaterials, hydrogels are emerging as a promising platform to address these limitations by enabling localized, controllable drug delivery and immunomodulation. This review systematically categorizes contemporary hydrogel construction strategies tailored for immunotherapy, highlighting the distinct advantages of specific architectures in diverse clinical contexts. By classifying hydrogel applications according to immune-based strategies, the work underscores their multifunctional utility as precision delivery platforms and modulators of the immune microenvironment. This comprehensive overview elucidates the progress and design principles of hydrogel-based immunotherapeutic platforms, providing valuable insights to guide future research and development in this evolving field.

Keywords

biomaterial / cancer / hydrogel / immunotherapy

References

[1] Y. Zhang, W. Zhang, Y. Wang, et al., “Emerging Nanotaxanes for Cancer Therapy,” Biomaterials 272 (2021): 120790.

[2] A. Lahiri, A. Maji, P. D. Potdar, et al., “Lung Cancer Immunotherapy: Progress, Pitfalls, and Promises,” Molecular Cancer 22, no. 1 (2023): 40.

[3] Y. Wang, M. Wang, H. X. Wu, and R. H. Xu, “Advancing to the Era of Cancer Immunotherapy,” Cancer Communications 41, no. 9 (2021): 803–829.

[4] K. K. Patel, M. Tariveranmoshabad, S. Kadu, N. Shobaki, and C. June, “From Concept to Cure: The Evolution of CAR-T Cell Therapy,” Molecular Therapy 33, no. 5 (2025): 2123–2140.

[5] L. W. Elmore, S. F. Greer, E. C. Daniels, et al., “Blueprint for Cancer Research: Critical Gaps and Opportunities,” CA: A Cancer Journal for Clinicians 71, no. 2 (2021): 107–139.

[6] H. Dong, Q. Li, Y. Zhang, M. Ding, Z. Teng, and Y. Mou, “Biomaterials Facilitating Dendritic Cell-mediated Cancer Immunotherapy,” Advanced Science 10, no. 18 (2023): 2301339.

[7] J. Yang, Y. Chen, L. Zhao, J. Zhang, and H. Luo, “Constructions and Properties of Physically Cross-linked Hydrogels Based on Natural Polymers,” Polymer Reviews 63, no. 3 (2023): 574–612.

[8] N. Richbourg, M. Wancura, A. Gilchrist, et al., “Precise Control of Synthetic Hydrogel Network Structure via Linear, Independent Synthesis-swelling Relationships,” Science Advances 7, no. 7 (2021): eabe3245.

[9] Z. Zhang, C. He, and X. Chen, “Designing Hydrogels for Immunomodulation in Cancer Therapy and Regenerative Medicine,” Advanced Materials 36, no. 4 (2024): 2308894.

[10] P. Lu, D. Ruan, M. Huang, et al., “Harnessing the Potential of Hydrogels for Advanced Therapeutic Applications: Current Achievements and Future Directions,” Signal Transduction and Targeted Therapy 9, no. 1 (2024): 166.

[11] C. Feng, Q. Wang, S. Xiao, et al., “Biopolymer Hydrogels for Adaptive Remodeling of the Tumor Microenvironment to Improve Cancer Immunotherapy,” Advanced Functional Materials (2025): e11828.

[12] Y. Wu, Y. Xiao, B. Yin, and S. H. D. Wong, “Dynamic Hydrogels: Adaptive Biomaterials for Engineering Tumor Microenvironment and Cancer Treatment,” International Journal of Molecular Sciences 26, no. 19 (2025): 9502.

[13] F. Xu, C. Dawson, M. Lamb, et al., “Hydrogels for Tissue Engineering: Addressing Key Design Needs Toward Clinical Translation,” Frontiers in Bioengineering and Biotechnology 10 (2022): 849831.

[14] Z. Wang, X. Wang, W. Xu, et al., “Translational Challenges and Prospective Solutions in the Implementation of Biomimetic Delivery Systems,” Pharmaceutics 15, no. 11 (2023): 2623.

[15] S. Correa, A. K. Grosskopf, H. Lopez Hernandez, et al., “Translational Applications of Hydrogels,” Chemical Reviews 121, no. 18 (2021): 11385–11457.

[16] S. Amirthalingam, A. K. Rajendran, Y. G. Moon, and N. S. Hwang, “Stimuli-responsive Dynamic Hydrogels: Design, Properties and Tissue Engineering Applications,” Materials Horizons 10, no. 9 (2023): 3325–3350.

[17] F. A. Carey and R. J. Sundberg, Advanced Organic Chemistry: Part A: Structure and Mechanisms (Springer Science & Business Media, 2007).

[18] X. Sun, D. Liu, X. Xu, et al., “NIR-triggered Thermo-responsive Biodegradable Hydrogel With Combination of Photothermal and Thermodynamic Therapy for Hypoxic Tumor,” Asian Journal of Pharmaceutical Sciences 15, no. 6 (2020): 713–727.

[19] S. H. Lee, Y. Lee, Y. W. Chun, et al., “In Situ Crosslinkable Gelatin Hydrogels for Vasculogenic Induction and Delivery of Mesenchymal Stem Cells,” Advanced Functional Materials 24, no. 43 (2014): 6771–6781.

[20] H. S. Seo, J. H. Han, J. Lim, et al., “Enhanced Postsurgical Cancer Treatment Using Methacrylated Glycol Chitosan Hydrogel for Sustained DNA/Doxorubicin Delivery and Immunotherapy,” Biomaterials Research 28 (2024): 0008.

[21] S. A. Meenach, J. Z. Hilt, and K. W. Anderson, “Poly(ethylene glycol)-based Magnetic Hydrogel Nanocomposites for Hyperthermia Cancer Therapy,” Acta Biomaterialia 6, no. 3 (2010): 1039–1046.

[22] Y. Che, D. Li, Y. Liu, et al., “Physically Cross-linked pH-responsive Chitosan-based Hydrogels With Enhanced Mechanical Performance for Controlled Drug Delivery,” RSC Advances 6, no. 107 (2016): 106035–106045.

[23] Y. N. Du, Q. Wei, L. J. Zhao, et al., “Hydrogel-based co-delivery of CIK Cells and Oncolytic adenovirus Armed With IL12 and IL15 for Cancer Immunotherapy,” Biomedicine & Pharmacotherapy 151 (2022): 113110.

[24] R. Steudel, “Properties of Sulfur-sulfur Bonds,” Angewandte Chemie International Edition in English 14, no. 10 (1975): 655–664.

[25] C. Shen, P. Zhang, Q. Sun, S. Bai, T. A. Hor, and X. Liu, “Recent Advances in C–S Bond Formation via C–H Bond Functionalization and Decarboxylation,” Chemical Society Reviews 44, no. 1 (2015): 291–314.

[26] J. Lou, Q. Wang, P. Wu, H. Wang, Y.-G. Zhou, and Z. Yu, “Transition-metal Mediated Carbon–sulfur Bond Activation and Transformations: An Update,” Chemical Society Reviews 49, no. 13 (2020): 4307–4359.

[27] L. Wang, W. He, and Z. Yu, “Transition-metal Mediated Carbon–sulfur Bond Activation and Transformations,” Chemical Society Reviews 42, no. 2 (2013): 599–621.

[28] D. Berne, V. Ladmiral, E. Leclerc, and S. Caillol, “Thia-Michael Reaction: The Route to Promising Covalent Adaptable Networks,” Polymers 14, no. 20 (2022): 4457.

[29] V. G. Muir and J. A. Burdick, “Chemically Modified Biopolymers for the Formation of Biomedical Hydrogels,” Chemical Reviews 121, no. 18 (2020): 10908–10949.

[30] R. Wang, Q. Hu, S. Huang, et al., “Zwitterionic Injectable Hydrogel-combined Chemo-and Immunotherapy Medicated by Monomolecular Micelles to Effectively Prevent the Recurrence of Tumor post Operation,” ACS Applied Materials & Interfaces 16, no. 3 (2024): 4071–4088.

[31] N. K. Livingston, J. W. Hickey, H. Sim, et al., “In Vivo Stimulation of Therapeutic Antigen-Specific T Cells in an Artificial Lymph Node Matrix,” Advanced Materials 36 (2024): e2310043.

[32] R. Ran, W. Shi, Y. Gao, et al., “Super-fast in Situ Formation of Hydrogels Based on Multi-arm Functional Polyethylene Glycols as Endotamponade Substitutes,” Journal of Materials Chemistry B 9, no. 44 (2021): 9162–9173.

[33] K. Li, X. Ju, X. Li, et al., “In Situ Formed Antibacterial Hydrogel With Collagenase-responsive Activity for Prevention of MRSA-induced Osteomyelitis,” Chemical Engineering Journal 489 (2024): 151475.

[34] B. Zhuang, T. Chen, Y. Huang, Z. Xiao, and Y. Jin, “Chemo-photothermal Immunotherapy for Eradication of Orthotopic Tumors and Inhibition of Metastasis by Intratumoral Injection of Polydopamine Versatile Hydrogels,” Acta Pharmaceutica Sinica B 12, no. 3 (2022): 1447–1459.

[35] J. Yan, Z. Zhang, X. Zhan, et al., “In Situ Injection of Dual-delivery PEG Based MMP-2 Sensitive Hydrogels for Enhanced Tumor Penetration and Chemo-immune Combination Therapy,” Nanoscale 13, no. 21 (2021): 9577–9589.

[36] K. M. Cook and P. J. Hogg, “Post-translational Control of Protein Function by Disulfide Bond Cleavage,” Antioxidants & Redox Signaling 18, no. 15 (2013): 1987–2015.

[37] L. Teng, Y. Chen, Y.-G. Jia, and L. Ren, “Supramolecular and Dynamic Covalent Hydrogel Scaffolds: From Gelation Chemistry to Enhanced Cell Retention and Cartilage Regeneration,” Journal of Materials Chemistry B 7, no. 43 (2019): 6705–6736.

[38] M. Zhang, W. Choi, M. Kim, et al., “Recent Advances in Environmentally Friendly Dual-crosslinking Polymer Networks,” Angewandte Chemie International Edition 63, no. 24 (2024): e202318035.

[39] X. Yang, B. Zhang, J. Li, et al., “Self-healing, Self-adhesive, and Stretchable Conductive Hydrogel for Multifunctional Sensor Prepared by Catechol Modified Nanocellulose Stabilized Poly (α-thioctic acid),” Carbohydrate Polymers 313 (2023): 120813.

[40] H. Ling, Y. Shen, L. Xu, et al., “Preparation and Characterization of Dual-network Interpenetrating Structure Hydrogels With Shape Memory and Self-healing Properties,” Colloids and Surfaces A: Physicochemical and Engineering Aspects 636 (2022): 128061.

[41] M. Chen, X. Ren, L. Dong, X. Li, and H. Cheng, “Preparation of Dynamic Covalently Crosslinking Keratin Hydrogels Based on Thiol/Disulfide Bonds Exchange Strategy,” International Journal of Biological Macromolecules 182 (2021): 1259–1267.

[42] R. Kilic Boz, D. Aydin, S. Kocak, B. Golba, R. Sanyal, and A. Sanyal, “Redox-responsive Hydrogels for Tunable and, “on-demand” Release of Biomacromolecules,” Bioconjugate Chemistry 33, no. 5 (2022): 839–847.

[43] K. Xu, H. Yao, D. Fan, L. Zhou, and S. Wei, “Hyaluronic Acid Thiol Modified Injectable Hydrogel: Synthesis, Characterization, Drug Release, Cellular Drug Uptake and Anticancer Activity,” Carbohydrate Polymers 254 (2021): 117286.

[44] F. X. Rwandamuriye, C. W. Evans, B. Wylie, et al., “A Surgically Optimized Intraoperative Poly (I: C)-releasing Hydrogel Prevents Cancer Recurrence,” Cell Reports Medicine 4, no. 7 (2023): 101113.

[45] L. A. Pérez, R. Hernández, J. M. Alonso, R. Pérez-González, and V. Sáez-Martínez, “Granular Disulfide-crosslinked Hyaluronic Hydrogels: A Systematic Study of Reaction Conditions on Thiol Substitution and Injectability Parameters,” Polymers 15, no. 4 (2023): 966.

[46] X. Jing, H. Hu, Y. Sun, B. Yu, H. Cong, and Y. Shen, “The Intracellular and Extracellular Microenvironment of Tumor Site: The Trigger of Stimuli-responsive Drug Delivery Systems,” Small Methods 6, no. 3 (2022): 2101437.

[47] S. Ulrich, “Growing Prospects of Dynamic Covalent Chemistry in Delivery Applications,” Accounts of Chemical Research 52, no. 2 (2019): 510–519.

[48] Y. Gao, K. Peng, and S. Mitragotri, “Covalently Crosslinked Hydrogels via Step-Growth Reactions: Crosslinking Chemistries, Polymers, and Clinical Impact,” Advanced Materials 33, no. 25 (2021): e2006362.

[49] M. E. Belowich and J. F. Stoddart, “Dynamic Imine Chemistry,” Chemical Society Reviews 41, no. 6 (2012): 2003–2024.

[50] M. R. Arkenberg, H. D. Nguyen, and C. C. Lin, “Recent Advances in Bio-orthogonal and Dynamic Crosslinking of Biomimetic Hydrogels,” Journal of Materials Chemistry B 8, no. 35 (2020): 7835–7855.

[51] Z. Zhang, C. He, and X. Chen, “Hydrogels Based on pH-responsive Reversible Carbon–nitrogen Double-bond Linkages for Biomedical Applications,” Materials Chemistry Frontiers 2, no. 10 (2018): 1765–1778.

[52] J. Gu, G. Zhao, J. Yu, et al., “Injectable pH-responsive Hydrogel for Combinatorial Chemoimmunotherapy Tailored to the Tumor Microenvironment,” Journal of Nanobiotechnology 20, no. 1 (2022): 372.

[53] L. Chang, R. Chang, J. Shen, et al., “Self-healing Pectin/Cellulose Hydrogel Loaded With Limonin as TMEM16A Inhibitor for Lung Adenocarcinoma Treatment,” International Journal of Biological Macromolecules 219 (2022): 754–766.

[54] R. Sun, Y. Chen, Q. Yang, W. Zhang, L. Guo, and M. Feng, “Polysaccharide Hydrogels Regulate Macrophage Polarization and Enhance the Anti-tumor Efficacy of Melanoma,” International Journal of Pharmaceutics 613 (2022): 121390.

[55] T. Liu, X. Si, L. Liu, et al., “Injectable Nano-in-Gel Vaccine for Spatial and Temporal Control of Vaccine Kinetics and Breast Cancer Postsurgical Therapy,” ACS Nano 18, no. 4 (2024): 3087–3100.

[56] G. Guedes, S. Wang, F. Fontana, et al., “Dual-Crosslinked Dynamic Hydrogel Incorporating Mo(154) With pH and NIR Responsiveness for Chemo-Photothermal Therapy,” Advanced Materials 33, no. 40 (2021): e2007761.

[57] T. He, X. Liang, L. Li, et al., “A Spontaneously Formed and Self-adjuvanted Hydrogel Vaccine Triggers Strong Immune Responses,” Materials & Design 197 (2021): 109232.

[58] K. Ishihara, “Dehydrative Condensation Catalyses,” Tetrahedron 65, no. 6 (2009): 1085–1109.

[59] E. Cordes and H. Bull, “Mechanism and Catalysis for Hydrolysis of Acetals, Ketals, and Ortho Esters,” Chemical Reviews 74, no. 5 (1974): 581–603.

[60] Y. Zhang, Q. Tang, J. Zhou, C. Zhao, J. Li, and H. Wang, “Conductive and Eco-friendly Biomaterials-based Hydrogels for Noninvasive Epidermal Sensors: A Review,” ACS Biomaterials Science & Engineering 10, no. 1 (2023): 191–218.

[61] X. Du, J. Zhou, J. Shi, and B. Xu, “Supramolecular Hydrogelators and Hydrogels: From Soft Matter to Molecular Biomaterials,” Chemical Reviews 115, no. 24 (2015): 13165–13307.

[62] E. C. Cheung and K. H. Vousden, “The Role of ROS in Tumour Development and Progression,” Nature Reviews Cancer 22, no. 5 (2022): 280–297.

[63] B. M. Sahoo, B. K. Banik, P. Borah, and A. Jain, “Reactive Oxygen Species (ROS): Key Components in Cancer Therapies,” Anti-Cancer Agents in Medicinal Chemistry-Anti-Cancer Agents 22, no. 2 (2022): 215–222.

[64] Y.-Y. Fan, H. Wu, and C. Xu, “ROS-Responsive Nanoplatforms for Targeted Tumor Immunomodulation: A Paradigm Shift in Precision Cancer Immunotherapy,” Pharmaceutics 17, no. 7 (2025): 886.

[65] Z. Sun, Y. Ding, Z. Wang, H. Luo, Q. Feng, and X. Cao, “Ros-responsive Hydrogel With Size-dependent Sequential Release Effects for Anti-bacterial and Anti-inflammation in Diabetic Wound Healing,” Chemical Engineering Journal 493 (2024): 152511.

[66] Y. Zhang, S. Tian, L. Huang, et al., “Reactive Oxygen Species-responsive and Raman-traceable Hydrogel Combining Photodynamic and Immune Therapy for Postsurgical Cancer Treatment,” Nature Communications 13, no. 1 (2022): 4553.

[67] Z. Dai, Q. Zhang, X. Li, et al., “In Situ Forming pH/ROS-responsive Niche-Like Hydrogel for Ultrasound-mediated Multiple Therapy in Synergy With Potentiating Anti-tumor Immunity,” Materials Today 65 (2023): 62–77.

[68] M.-Q. Tong, L.-Z. Luo, P.-P. Xue, et al., “Glucose-responsive Hydrogel Enhances the Preventive Effect of Insulin and Liraglutide on Diabetic Nephropathy of Rats,” Acta Biomaterialia 122 (2021): 111–132.

[69] S. Kim, J. Lee, S. Im, and W. J. Kim, “Injectable Immunogel Based on Polymerized Phenylboronic Acid and mannan for Cancer Immunotherapy,” Journal of Controlled Release 345 (2022): 138–146.

[70] M. Zhou, Q. Zuo, Y. Huang, and L. Li, “Immunogenic Hydrogel Toolkit Disturbing Residual Tumor, “Seeds” and Pre-metastatic, “Soil” for Inhibition of Postoperative Tumor Recurrence and Metastasis,” Acta Pharmaceutica Sinica B 12, no. 8 (2022): 3383–3397.

[71] J. R. Dunetz, J. Magano, and G. A. Weisenburger, “Large-scale Applications of Amide Coupling Reagents for the Synthesis of Pharmaceuticals,” Organic Process Research & Development 20, no. 2 (2016): 140–177.

[72] P. Suwattanachai, A. Pimkhaokham, and S. Chirachanchai, “Multi-functional Carboxylic Acids for Chitosan Scaffold,” International Journal of Biological Macromolecules 134 (2019): 156–164.

[73] X. Zheng, H. Wu, S. Wang, J. Zhao, and L. Hu, “Preparation and Characterization of Biocompatible Iron/Zirconium/Polydopamine/Carboxymethyl Chitosan Hydrogel With Fenton Catalytic Properties and Photothermal Efficacy,” Gels 9, no. 6 (2023): 452.

[74] Y. Bu, L. Zhang, G. Sun, et al., “Tetra-PEG Based Hydrogel Sealants for in Vivo Visceral Hemostasis,” Advanced Materials 31, no. 28 (2019): e1901580.

[75] I. Strehin, D. Gourevitch, Y. Zhang, E. Heber-Katz, and P. B. Messersmith, “Hydrogels Formed by Oxo-ester Mediated Native Chemical Ligation,” Biomaterials Science 1, no. 6 (2013): 603–613.

[76] Y. Yu, X. Zheng, X. Liu, J. Zhao, and S. Wang, “Injectable Carboxymethyl Chitosan-based Hydrogel for Simultaneous Anti-tumor Recurrence and Anti-bacterial Applications,” International Journal of Biological Macromolecules 230 (2023): 123196.

[77] H. Wang, Y. Chen, R. Wei, et al., “Synergistic Chemoimmunotherapy Augmentation via Sequential Nanocomposite Hydrogel-Mediated Reprogramming of Cancer-Associated Fibroblasts in Osteosarcoma,” Advanced Materials 36, no. 15 (2024): e2309591.

[78] M. Lubberink, W. Finnigan, and S. L. Flitsch, “Biocatalytic Amide Bond Formation,” Green Chemistry 25, no. 8 (2023): 2958–2970.

[79] P. V. Bernhardt and G. A. Lawrance, Introduction to Coordination Chemistry (John Wiley & Sons, 2025).

[80] M. Deshmukh, Y. Singh, S. Gunaseelan, D. Gao, S. Stein, and P. J. Sinko, “Biodegradable Poly (ethylene glycol) Hydrogels Based on a Self-elimination Degradation Mechanism,” Biomaterials 31, no. 26 (2010): 6675–6684.

[81] R. K. Sigel and H. Sigel, “A Stability Concept for Metal Ion Coordination to Single-stranded Nucleic Acids and Affinities of Individual Sites,” Accounts of Chemical Research 43, no. 7 (2010): 974–984.

[82] Y. Cao, Y. Zhou, J. Pan, et al., “A General Strategy towards an Injectable Microwave-sensitive Immune Hydrogel for Combined Percutaneous Microwave Ablation and Immunotherapy,” Chemical Engineering Journal 422 (2021): 130111.

[83] Y. Yang, Y. Ma, M. Wu, et al., “Fe3+-induced Coordination Cross-linking Gallic Acid-carboxymethyl Cellulose Self-healing Hydrogel,” International Journal of Biological Macromolecules 267 (2024): 131626.

[84] W. Shen, P. Pei, C. Zhang, et al., “A Polymeric Hydrogel to Eliminate Programmed Death-ligand 1 for Enhanced Tumor Radio-immunotherapy,” ACS Nano 17, no. 23 (2023): 23998–24011.

[85] L. Wu, W. Pi, X. Huang, et al., “Orchestrated Metal-coordinated Carrier-free Celastrol Hydrogel Intensifies T Cell Activation and Regulates Response to Immune Checkpoint Blockade for Synergistic Chemo-immunotherapy,” Biomaterials 312 (2025): 122723.

[86] K. Y. Wong, Z. Nie, M. S. Wong, Y. Wang, and J. Liu, “Metal–drug Coordination Nanoparticles and Hydrogels for Enhanced Delivery,” Advanced Materials 36, no. 26 (2024): 2404053.

[87] A. Charlet, V. Lutz-Bueno, R. Mezzenga, and E. Amstad, “Shape Retaining Self-healing Metal-coordinated Hydrogels,” Nanoscale 13, no. 7 (2021): 4073–4084.

[88] E. S. Dragan and M. V. Dinu, “Polysaccharides Constructed Hydrogels as Vehicles for Proteins and Peptides. A Review,” Carbohydrate Polymers 225 (2019): 115210.

[89] H. Ohshima, “Electrostatic Interaction of Soft Particles,” Advances in Colloid and Interface Science 226 (2015): 2–16.

[90] S. Duan, M. Hua, C. W. Zhang, et al., “Noncovalent Aggregation for Diverse Properties in Hydrogels: A Comprehensive Review,” Chemical Reviews 125, no. 16 (2025): 7918–7964.

[91] L. Lei, Y. Bai, X. Qin, J. Liu, W. Huang, and Q. Lv, “Current Understanding of Hydrogel for Drug Release and Tissue Engineering,” Gels 8, no. 5 (2022): 301.

[92] A. Sadraei and S. M. Naghib, “4D printing of Physical Stimuli-responsive Hydrogels for Localized Drug Delivery and Tissue Engineering,” Polymer Reviews 65, no. 1 (2025): 104–168.

[93] J. Ma, X. He, L. Wang, and J. Pang, “Magnetic Fucoidan Aerogel Microspheres: Cationic Drug Loading Kinetics and Electrostatic-Magnetic Synergy,” Colloids and Surfaces A: Physicochemical and Engineering Aspects 726 (2025): 137843.

[94] N. Falcone, M. Ermis, A. Gangrade, et al., “Drug-Eluting Shear-Thinning Hydrogel for the Delivery of Chemo-and Immunotherapeutic Agents for the Treatment of Hepatocellular Carcinoma,” Advanced Functional Materials 34, no. 8 (2024): 2309069.

[95] K. Teng, Q. An, Y. Chen, Y. Zhang, and Y. Zhao, “Recent Development of Alginate-based Materials and Their Versatile Functions in Biomedicine, Flexible Electronics, and Environmental Uses,” ACS Biomaterials Science & Engineering 7, no. 4 (2021): 1302–1337.

[96] T. Xiao, J. Zhu, L. Jia, et al., “Injectable Alginate Hydrogels for Synergistic Tumor Combination Therapy Through Repolarization of Tumor-associated Macrophages,” Journal of Controlled Release 348 (2022): 239–249.

[97] L. Sun, F. Shen, L. Tian, et al., “ATP-responsive Smart Hydrogel Releasing Immune Adjuvant Synchronized With Repeated Chemotherapy or Radiotherapy to Boost Antitumor Immunity,” Advanced Materials 33, no. 18 (2021): 2007910.

[98] K. Li, X. Yu, Y. Xu, et al., “Cascaded Immunotherapy With Implantable Dual-drug Depots Sequentially Releasing STING Agonists and Apoptosis Inducers,” Nature Communications 16, no. 1 (2025): 1629.

[99] X. Xue, Y. Hu, Y. Deng, and J. Su, “Recent Advances in Design of Functional Biocompatible Hydrogels for Bone Tissue Engineering,” Advanced Functional Materials 31, no. 19 (2021): 2009432.

[100] P. Bertsch, M. Diba, D. J. Mooney, and S. C. Leeuwenburgh, “Self-healing Injectable Hydrogels for Tissue Regeneration,” Chemical Reviews 123, no. 2 (2022): 834–873.

[101] E. Pishavar, F. Khosravi, M. Naserifar, et al., “Multifunctional and Self-healable Intelligent Hydrogels for Cancer Drug Delivery and Promoting Tissue Regeneration in Vivo,” Polymers 13, no. 16 (2021): 2680.

[102] P. Chen, C. Yu, J. Chen, L. Xu, and H. Liu, “DNA-based Supramolecular Hydrogels: From Construction Strategies to Biomedical Applications,” Chinese Chemical Letters 34, no. 12 (2023): 108627.

[103] R. Zhang, Z. Lv, L. Chang, et al., “A Responsive DNA Hydrogel Containing Poly-Aptamers as Dual-Target Inhibitors for Localized Cancer Immunotherapy,” Advanced Functional Materials 34, no. 32 (2024): 2401563.

[104] F. Wang, M. Xie, Y. Huang, et al., “In Situ Vaccination With an Injectable Nucleic Acid Hydrogel for Synergistic Cancer Immunotherapy,” Angewandte Chemie (International ed in English) 63, no. 4 (2024): e202315282.

[105] Y. Zhao, J. Du, Z. Xu, L. Wang, L. Ma, and L. Sun, “DNA Adjuvant Hydrogel-Optimized Enzymatic Cascade Reaction for Tumor Chemodynamic-Immunotherapy,” Advanced Science (Weinheim) 11, no. 10 (2024): e2308229.

[106] Z. Li, W. Xu, J. Yang, et al., “A Tumor Microenvironments-Adapted Polypeptide Hydrogel/Nanogel Composite Boosts Antitumor Molecularly Targeted Inhibition and Immunoactivation,” Advanced Materials 34, no. 21 (2022): e2200449.

[107] Q. Song, G. Lan, Q. Li, et al., “A Hydrogel-enabled Cascade Amplification of Radiosensitization and Immune Activation for Cancer Radiotherapy,” Chemical Engineering Journal 462 (2023): 142201.

[108] S. Tiamwong, P. Yukhajon, P. Noisong, M. Subsadsana, and S. Sansuk, “Eco-Friendly Starch Composite Supramolecular Alginate-Ca(2+) Hydrogel as Controlled-Release P Fertilizer With Low Responsiveness to Multiple Environmental Stimuli,” Gels 9, no. 3 (2023): 204.

[109] Y. Wu, Y. Shi, and H. Wang, “Urea as a Hydrogen Bond Producer for Fabricating Mechanically Very Strong Hydrogels,” Macromolecules 56, no. 12 (2023): 4491–4502.

[110] E. C. de Siqueira, J. A. A. de França, R. F. M. de Souza, et al., “Recent Advances in the Development of the Physically Crosslinked Hydrogels and Their Biomedical Applications,” Research, Society and Development 12, no. 8 (2023): e18212843073–e18212843073.

[111] Y. Ma, X. Duan, and J. Huang, “DNA Hydrogels as Functional Materials and Their Biomedical Applications,” Advanced Functional Materials 34, no. 3 (2024): 2309070.

[112] Y. Li, R. Chen, B. Zhou, Y. Dong, and D. Liu, “Rational Design of DNA Hydrogels Based on Molecular Dynamics of Polymers,” Advanced Materials 36, no. 7 (2024): 2307129.

[113] J. A. Villegas, M. Heidenreich, and E. D. Levy, “Molecular and Environmental Determinants of Biomolecular Condensate Formation,” Nature Chemical Biology 18, no. 12 (2022): 1319–1329.

[114] M. Gosecka, M. Gosecki, and D. Jaworska-Krych, “Hydrophobized Hydrogels: Construction Strategies, Properties, and Biomedical Applications,” Advanced Functional Materials 33, no. 25 (2023): 2212302.

[115] K. Ren, X. Quanji, X. Du, C. Cai, J. Luo, and J. Yin, “Hydrogen Bond and Hydrophobic Interaction Reinforced Tough and Antiswelling Hydrogels via Polymerization-Induced Microphase Separation,” Biomacromolecules 26, no. 6 (2025): 3868–3878.

[116] W. Feng and Z. Wang, “Tailoring the Swelling-shrinkable Behavior of Hydrogels for Biomedical Applications,” Advanced Science 10, no. 28 (2023): 2303326.

[117] A. Lupu, I. Rosca, V. R. Gradinaru, and M. Bercea, “Temperature Induced Gelation and Antimicrobial Properties of Pluronic F127 Based Systems,” Polymers 15, no. 2 (2023): 355.

[118] N. A. Di Spirito, N. Grizzuti, and R. Pasquino, “Self-assembly of Pluronics: A Critical Review and Relevant Applications,” Physics of Fluids 36, no. 11 (2024): 111302.

[119] J. Kim, D. M. Francis, L. F. Sestito, et al., “Thermosensitive Hydrogel Releasing Nitric Oxide Donor and Anti-CTLA-4 Micelles for Anti-tumor Immunotherapy,” Nature Communications 13, no. 1 (2022): 1479.

[120] M. Fan, L. Jia, M. Pang, et al., “Injectable Adhesive Hydrogel as Photothermal-derived Antigen Reservoir for Enhanced Anti-tumor Immunity,” Advanced Functional Materials 31, no. 20 (2021): 2010587.

[121] Z. Li, L. Yang, D. Zhang, et al., “Mussel-inspired, “Plug-and-play” Hydrogel Glue for Postoperative Tumor Recurrence and Wound Infection Inhibition,” Journal of Colloid & Interface Science 650, no. Pt B (2023): 1907–1917.

[122] X. Meng, Z. Liu, Y. Yang, et al., “Engineered Microcystis Aerugiosa Hydrogel as an Anti-Tumor Therapeutic by Augmenting Tumor Immunogenicity and Immune Responses,” Advanced Functional Materials 34, no. 7 (2023): 2305915.

[123] M. Nichifor, “Role of Hydrophobic Associations in Self-healing Hydrogels Based on Amphiphilic Polysaccharides,” Polymers 15, no. 5 (2023): 1065.

[124] Y. P. Jia, K. Shi, F. Yang, et al., “Multifunctional Nanoparticle Loaded Injectable Thermoresponsive Hydrogel as NIR Controlled Release Platform for Local Photothermal Immunotherapy to Prevent Breast Cancer Postoperative Recurrence and Metastases,” Advanced Functional Materials 30, no. 25 (2020): 2001059.

[125] Y. Shi, D. Li, C. He, and X. Chen, “Design of an Injectable Polypeptide Hydrogel Depot Containing the Immune Checkpoint Blocker Anti-PD-L1 and Doxorubicin to Enhance Antitumor Combination Therapy,” Macromolecular Bioscience 21, no. 6 (2021): 2100049.

[126] Y. Jiang, N. Tang, X. Wang, et al., “Mechanically Robust Eutectogels Enabled by Precisely Engineered Crystalline Domains,” Nature Communications 16, no. 1 (2025): 7417.

[127] J. Ren, G. Chen, H. Yang, et al., “Super-Tough, Non-Swelling Zwitterionic Hydrogel Sensor Based on the Hofmeister Effect for Potential Motion Monitoring of Marine Animals,” Advanced Materials 36, no. 48 (2024): 2412162.

[128] P. Jiang, P. Lin, C. Yang, H. Qin, X. Wang, and F. Zhou, “3D printing of Dual-physical Cross-linking Hydrogel With Ultrahigh Strength and Toughness,” Chemistry of Materials 32, no. 23 (2020): 9983–9995.

[129] E. A. Appel, J. del Barrio, X. J. Loh, and O. A. Scherman, “Supramolecular Polymeric Hydrogels,” Chemical Society Reviews 41, no. 18 (2012): 6195–6214.

[130] Q.-D. Hu, G.-P. Tang, and P. K. Chu, “Cyclodextrin-based Host–guest Supramolecular Nanoparticles for Delivery: From Design to Applications,” Accounts of Chemical Research 47, no. 7 (2014): 2017–2025.

[131] S. Tan, K. Ladewig, Q. Fu, A. Blencowe, and G. G. Qiao, “Cyclodextrin-based Supramolecular Assemblies and Hydrogels: Recent Advances and Future Perspectives,” Macromolecular Rapid Communications 35, no. 13 (2014): 1166–1184.

[132] G. Crini, S. Fourmentin, É. Fenyvesi, G. Torri, M. Fourmentin, and N. Morin-Crini, “Cyclodextrins, From Molecules to Applications,” Environmental Chemistry Letters 16 (2018): 1361–1375.

[133] A. Yang, Y. Bai, X. Dong, et al., “Hydrogel/Nanoadjuvant-mediated Combined Cell Vaccines for Cancer Immunotherapy,” Acta Biomaterialia 133 (2021): 257–267.

[134] Z. Xu, L. Liu, J. Duan, et al., “A Host/Guest Assembled Hyaluronic Acid-based Supramolecular Hydrogel With NIR-steered Degradation Capacity for Enhanced Tumor Therapy Through Programmable Drug Release,” Carbohydrate Polymers 368, no. Pt 1 (2025): 124098.

[135] K. Xu, Y. Wen, X. Zhang, et al., “Injectable Host-guest Gel Nanovaccine for Cancer Immunotherapy Against Melanoma,” Materials Today Advances 15 (2022): 100236.

[136] C. Zhu, L. Ke, X. Ao, et al., “Injectable Supramolecular Hydrogels for in Situ Programming of Car-T Cells Toward Solid Tumor Immunotherapy,” Advanced Materials 36, no. 5 (2024): 2310078.

[137] C. Xu, Y. Chen, S. Zhao, et al., “Mechanical Regulation of Polymer Gels,” Chemical Reviews 124, no. 18 (2024): 10435–10508.

[138] G. Fang, X. Yang, S. Chen, Q. Wang, A. Zhang, and B. Tang, “Cyclodextrin-based Host–guest Supramolecular Hydrogels for Local Drug Delivery,” Coordination Chemistry Reviews 454 (2022): 214352.

[139] W. Hu, Z. Wang, Y. Xiao, S. Zhang, and J. Wang, “Advances in Crosslinking Strategies of Biomedical Hydrogels,” Biomaterials Science 7, no. 3 (2019): 843–855.

[140] K. Zhang, Q. Feng, Z. Fang, L. Gu, and L. Bian, “Structurally Dynamic Hydrogels for Biomedical Applications: Pursuing a Fine Balance Between Macroscopic Stability and Microscopic Dynamics,” Chemical Reviews 121, no. 18 (2021): 11149–11193.

[141] S. Dong, S. An, and Q. Saiding, “Therapeutic Hydrogels: Properties and Biomedical Applications,” Chemical Reviews 125, no. 18 (2025): 8835–8920.

[142] X. Lin, X. Zhao, C. Xu, L. Wang, and Y. Xia, “Progress in the Mechanical Enhancement of Hydrogels: Fabrication Strategies and Underlying Mechanisms,” Journal of Polymer Science 60, no. 17 (2022): 2525–2542.

[143] J. Lou and D. J. Mooney, “Chemical Strategies to Engineer Hydrogels for Cell Culture,” Nature Reviews Chemistry 6, no. 10 (2022): 726–744.

[144] Y. Feng, Z. Zhang, W. Tang, and Y. Dai, Gel/Hydrogel-based in Situ Biomaterial Platforms for Cancer Postoperative Treatment and Recovery (Wiley Online Library, 2023): 20220173.

[145] J. Zhao, L. Wang, H. Zhang, B. Liao, and Y. Li, “Progress of Research in in Situ Smart Hydrogels for Local Antitumor Therapy: A Review,” Pharmaceutics 14, no. 10 (2022): 2028.

[146] Z. Wang, B. Zhai, J. Sun, et al., “Recent Advances of Injectable in Situ-forming Hydrogels for Preventing Postoperative Tumor Recurrence,” Drug Delivery 31, no. 1 (2024): 2400476.

[147] N. Eckman, A. Nejatfard, R. Cavet, A. K. Grosskopf, and E. A. Appel, “Biomaterials to Enhance Adoptive Cell Therapy,” Nature Reviews Bioengineering 2, no. 5 (2024): 408–424.

[148] H. Wang, R. Huang, L. Bai, et al., “Extracellular Matrix-Mimetic Immunomodulatory Hydrogel for Accelerating Wound Healing,” Advanced Healthcare Materials 12, no. 27 (2023): 2301264.

[149] Z. Li, F. Lu, and Y. Liu, “A Review of the Mechanism, Properties, and Applications of Hydrogels Prepared by Enzymatic Cross-linking,” Journal of Agricultural and Food Chemistry 71, no. 27 (2023): 10238–10249.

[150] M. Li, N. T. Blum, J. Wu, J. Lin, and P. Huang, “Weaving Enzymes With Polymeric Shells for Biomedical Applications,” Advanced Materials 33, no. 34 (2021): 2008438.

[151] M. Rodin, J. Li, and D. Kuckling, “Dually Cross-linked Single Networks: Structures and Applications,” Chemical Society Reviews 50, no. 14 (2021): 8147–8177.

[152] A. Zhang, T. Fan, Y. Liu, G. Yu, C. Li, and Z. Jiang, “Regulatory T Cells in Immune Checkpoint Blockade Antitumor Therapy,” Molecular Cancer 23, no. 1 (2024): 251.

[153] G. Liu, W. Rui, X. Zhao, and X. Lin, “Enhancing CAR-T Cell Efficacy in Solid Tumors by Targeting the Tumor Microenvironment,” Cellular & Molecular Immunology 18, no. 5 (2021): 1085–1095.

[154] B. Pulendran, P. S Arunachalam, and D. T. O'Hagan, “Emerging Concepts in the Science of Vaccine Adjuvants,” Nature Reviews Drug Discovery 20, no. 6 (2021): 454–475.

[155] S. B. Ebrahimi and D. Samanta, “Engineering Protein-based Therapeutics Through Structural and Chemical Design,” Nature Communications 14, no. 1 (2023): 2411.

[156] L.-C. Tsao, J. Force, and Z. C. Hartman, “Mechanisms of Therapeutic Antitumor Monoclonal Antibodies,” Cancer Research 81, no. 18 (2021): 4641–4651.

[157] D. Yadav, M. Kwak, P. S. Chauhan, N. Puranik, P. C. Lee, and J.-O. Jin, Cancer Immunotherapy by Immune Checkpoint Blockade and Its Advanced Application Using Bio-nanomaterials (Elsevier, 2022): 909–922.

[158] J. Deckers, T. Anbergen, A. M. Hokke, et al., “Engineering Cytokine Therapeutics,” Nature Reviews Bioengineering 1, no. 4 (2023): 286–303.

[159] Y. Song, L. Lei, X. Cai, H. Wei, and C. Y. Yu, “Immunomodulatory Peptides for Tumor Treatment,” Advanced Healthcare Materials 14, no. 5 (2025): 2400512.

[160] M. Muttenthaler, G. F. King, D. J. Adams, and P. F. Alewood, “Trends in Peptide Drug Discovery,” Nature Reviews Drug Discovery 20, no. 4 (2021): 309–325.

[161] K. C. Baral and K. Y. Choi, “Barriers and Strategies for Oral Peptide and Protein Therapeutics Delivery: Update on Clinical Advances,” Pharmaceutics 17, no. 4 (2025): 397.

[162] Y. Chen, I. Tandon, W. Heelan, Y. Wang, W. Tang, and Q. Hu, “Proteolysis-targeting Chimera (PROTAC) Delivery System: Advancing Protein Degraders towards Clinical Translation,” Chemical Society Reviews 51, no. 13 (2022): 5330–5350.

[163] H. Li, L. Yu, Z. Li, et al., “A Narrative Review of Bioactive Hydrogel Microspheres: Ingredients, Modifications, Fabrications, Biological Functions, and Applications,” Small 21 (2025): 2500426.

[164] Q. Zhu, Z. Chen, P. K. Paul, Y. Lu, W. Wu, and J. Qi, “Oral Delivery of Proteins and Peptides: Challenges, Status Quo and Future Perspectives,” Acta Pharmaceutica Sinica B 11, no. 8 (2021): 2416–2448.

[165] Z. Yang, D. J. McClements, C. Li, et al., “Targeted Delivery of Hydrogels in human Gastrointestinal Tract: A Review,” Food Hydrocolloids 134 (2023): 108013.

[166] M. Nicze, M. Borówka, A. Dec, A. Niemiec, Ł. Bułdak, and B. Okopień, “The Current and Promising Oral Delivery Methods for Protein-and Peptide-based Drugs,” International Journal of Molecular Sciences 25, no. 2 (2024): 815.

[167] J. Ouyang, B. Deng, B. Zou, et al., “Oral Hydrogel Microbeads-mediated in Situ Synthesis of Selenoproteins for Regulating Intestinal Immunity and Microbiota,” Journal of the American Chemical Society 145, no. 22 (2023): 12193–12205.

[168] J. Pattyn, G. Hendrickx, A. Vorsters, and P. Van Damme, “Hepatitis B Vaccines,” The Journal of Infectious Diseases 224, no. Supplement_4 (2021): S343–S351.

[169] M. K. Weng, “Universal hepatitis B Vaccination in Adults Aged 19–59 Years: Updated Recommendations of the Advisory Committee on Immunization Practices—United States, 2022,” MMWR Morbidity and Mortality Weekly Report 71, no. 13 (2022): 477–483.

[170] X. Y. Chen, A. M. Butt, and M. C. I. Mohd Amin, “Molecular Evaluation of Oral Immunogenicity of hepatitis B Antigen Delivered by Hydrogel Microparticles,” Molecular Pharmaceutics 16, no. 9 (2019): 3853–3872.

[171] M. A. Nauck, D. R. Quast, J. Wefers, and J. J. Meier, “GLP-1 Receptor Agonists in the Treatment of Type 2 Diabetes—state-of-the-art,” Molecular Metabolism 46 (2021): 101102.

[172] Y. Zhou, Z. Chen, D. Zhao, D. Li, C. He, and X. Chen, “A pH-triggered Self-unpacking Capsule Containing Zwitterionic Hydrogel-coated MOF Nanoparticles for Efficient Oral Exendin-4 Delivery,” Advanced Materials 33, no. 32 (2021): 2102044.

[173] R. Li, Y. He, S. Zhang, J. Qin, and J. Wang, “Cell Membrane-based Nanoparticles: A New Biomimetic Platform for Tumor Diagnosis and Treatment,” Acta Pharmaceutica Sinica B 8, no. 1 (2018): 14–22.

[174] X. Zhang, Y. Wu, J. Lin, et al., “Insights Into Therapeutic Peptides in the Cancer-immunity Cycle: Update and Challenges,” Acta Pharmaceutica Sinica B 14, no. 9 (2024): 3818–3833.

[175] M. M. Gomari, T. Ghantabpour, N. Pourgholam, et al., “Breaking Barriers: Smart Vaccine Platforms for Cancer Immunomodulation,” Cancer Communications 45, no. 5 (2025): 529–571.

[176] L. Lei, D. Huang, H. Gao, B. He, J. Cao, and N. A. Peppas, “Hydrogel-guided Strategies to Stimulate an Effective Immune Response for Vaccine-based Cancer Immunotherapy,” Science Advances 8, no. 47 (2022): eadc8738.

[177] Q. Chen, S. Zhou, Y. Ding, et al., “A Bio-responsive, Cargo-catchable Gel for Postsurgical Tumor Treatment via ICD-based Immunotherapy,” Journal of Controlled Release 346 (2022): 212–225.

[178] L. Ye, W. Lv, W. He, et al., “Reduced Malignant Glioblastoma Recurrence Post-resection Through the Anti-CD47 Antibody and Temozolomide co-embedded in-situ Hydrogel System,” Journal of Controlled Release 359 (2023): 224–233.

[179] T. R. Mempel, J. K. Lill, and L. M. Altenburger, “How Chemokines Organize the Tumour Microenvironment,” Nature Reviews Cancer 24, no. 1 (2024): 28–50.

[180] A. Goenka, F. Khan, B. Verma, et al., “Tumor Microenvironment Signaling and Therapeutics in Cancer Progression,” Cancer Communications 43, no. 5 (2023): 525–561.

[181] Y. Xiong, X. Zhang, X. Ma, et al., “A Review of the Properties and Applications of Bioadhesive Hydrogels,” Polymer Chemistry 12, no. 26 (2021): 3721–3739.

[182] C.-H. Lee, W.-Y. Huang, K.-Y. Lee, et al., “Bioinspired Adhesive Nanofibrous Hydrogel Promotes Immune Infiltration Through Effective Immunochemotherapy for Osteosarcoma Treatment,” Chemical Engineering Journal 486 (2024): 150236.

[183] A. K. Grosskopf, L. Labanieh, D. D. Klysz, et al., “Delivery of CAR-T Cells in a Transient Injectable Stimulatory Hydrogel Niche Improves Treatment of Solid Tumors,” Science Advances 8, no. 14 (2022): eabn8264.

[184] A. K. Tripathi and J. K. Vishwanatha, “Role of Anti-cancer Peptides as Immunomodulatory Agents: Potential and Design Strategy,” Pharmaceutics 14, no. 12 (2022): 2686.

[185] W. Zhang, S. Li, Y. Liu, et al., “Immunosuppressive Microenvironment Improvement and Treatment of Aggressive Malignancy Pancreatic Ductal Adenocarcinoma Based on Local Administration of Injectable Hydrogel,” Nano Today 50 (2023): 101832.

[186] Q. Geng, P. Jiao, P. Jin, G. Su, J. Dong, and B. Yan, “PD-1/PD-L1 Inhibitors for Immuno-oncology: From Antibodies to Small Molecules,” Current Pharmaceutical Design 23, no. 39 (2017): 6033–6041.

[187] M. Liu, Z. Cao, R. Zhang, Y. Chen, and X. Yang, “Injectable Supramolecular Hydrogel for Locoregional Immune Checkpoint Blockade and Enhanced Cancer Chemo-immunotherapy,” ACS Applied Materials & Interfaces 13, no. 29 (2021): 33874–33884.

[188] J. Kim, Y. Choi, D.-H. Kim, H. Y. Yoon, and K. Kim, “Injectable Hydrogel-based Combination Cancer Immunotherapy for Overcoming Localized Therapeutic Efficacy,” Pharmaceutics 14, no. 9 (2022): 1908.

[189] S. Aryal, “Antigen Properties, Types and Determinants of Antigenicity,” Microbiologyinfo.com; 2018.

[190] H. N. Eisen and A. K. Chakraborty, “Evolving Concepts of Specificity in Immune Reactions,” Proceedings of the National Academy of Sciences of the United States of America 107, no. 52 (2010): 22373–22380.

[191] M. M. Rana, C. Demirkaya, and H. De la Hoz Siegler, “Beyond Needles: Immunomodulatory Hydrogel-Guided Vaccine Delivery Systems,” Gels 11, no. 1 (2024): 7.

[192] O. S. Fenton, M. W. Tibbitt, E. A. Appel, S. Jhunjhunwala, M. J. Webber, and R. Langer, “Injectable Polymer–Nanoparticle Hydrogels for Local Immune Cell Recruitment,” Biomacromolecules 20, no. 12 (2019): 4430–4436.

[193] Y. Zhu, L. Jin, J. Chen, M. Su, T. Sun, and X. Yang, “Promoting the Recruitment, Engagement, and Reinvigoration of Effector T Cells via an Injectable Hydrogel With a Supramolecular Binding Capability for Cancer Immunotherapy,” Advanced Materials 35, no. 47 (2023): 2309667.

[194] E. Minaei, M. Ranson, M. Aghmesheh, R. Sluyter, and K. Vine, “Enhancing Pancreatic Cancer Immunotherapy: Leveraging Localized Delivery Strategies Through the Use of Implantable Devices and Scaffolds,” Journal of Controlled Release 373 (2024): 145–160.

[195] Y. Peng, S. Liang, Q. F. Meng, et al., “Engineered Bio-Based Hydrogels for Cancer Immunotherapy,” Advanced Materials 36, no. 21 (2024): 2313188.

[196] X. Liang, L. Li, X. Li, et al., “A Spontaneous Multifunctional Hydrogel Vaccine Amplifies the Innate Immune Response to Launch a Powerful Antitumor Adaptive Immune Response,” Theranostics 11, no. 14 (2021): 6936.

[197] S. Pant, Z. A. Wainberg, C. D. Weekes, et al., “Lymph-node-targeted, mKRAS-specific Amphiphile Vaccine in Pancreatic and Colorectal Cancer: The Phase 1 AMPLIFY-201 Trial,” Nature Medicine 30, no. 2 (2024): 531–542.

[198] G. Ma, F. Li, X. Wang, et al., “A Bionic Yeast Tumor Vaccine Using the co-loading Strategy to Prevent Post-operative Tumor Recurrence,” Acs Nano 17, no. 21 (2023): 21394–21410.

[199] G. A. Roth, E. C. Gale, M. Alcántara-Hernández, et al., “Injectable Hydrogels for Sustained Codelivery of Subunit Vaccines Enhance Humoral Immunity,” ACS Central Science 6, no. 10 (2020): 1800–1812.

[200] H. Phuengkham, C. Song, S. H. Um, and Y. T. Lim, “Implantable Synthetic Immune Niche for Spatiotemporal Modulation of Tumor-derived Immunosuppression and Systemic Antitumor Immunity: Postoperative Immunotherapy,” Advanced Materials 30, no. 18 (2018): 1706719.

[201] W. Liu, H. Tang, L. Li, X. Wang, Z. Yu, and J. Li, “Peptide-based Therapeutic Cancer Vaccine: Current Trends in Clinical Application,” Cell Proliferation 54, no. 5 (2021): e13025.

[202] A. Vaisman-Mentesh, M. Gutierrez-Gonzalez, B. J. DeKosky, and Y. Wine, “The Molecular Mechanisms That Underlie the Immune Biology of Anti-drug Antibody Formation Following Treatment With Monoclonal Antibodies,” Frontiers in Immunology 11 (2020): 1951.

[203] C. R. Parikh, J. K. Ponnampalam, G. Seligmann, et al., “Impact of Immunogenicity on Clinical Efficacy and Toxicity Profile of Biologic Agents Used for Treatment of Inflammatory Arthritis in Children Compared to Adults,” Therapeutic Advances in Musculoskeletal Disease 13 (2021): 1759720×211002685.

[204] F. Cheng, T. Su, S. Zhou, et al., “Single-dose Injectable Nanovaccine-in-hydrogel for Robust Immunotherapy of Large Tumors With Abscopal Effect,” Science Advances 9, no. 28 (2023): eade6257.

[205] Z. Xiong, L. Sun, H. Yang, et al., “Ni-Alginate Hydrogel Microspheres With Sustained Interleukin 2 Release to Boost Cytokine-based Cancer Immunotherapy,” Advanced Functional Materials 33, no. 7 (2023): 2211423.

[206] M. Gu, S. Sun, Q. You, and L. Wang, “Forward or Backward: Lessons Learned From Small Molecule Drugs Approved by FDA From 2012 to 2022,” Molecules (Basel, Switzerland) 28, no. 24 (2023): 7941.

[207] C. C. Ayala-Aguilera, T. Valero, Á. Lorente-Macías, D. J. Baillache, S. Croke, and A. Unciti-Broceta, “Small Molecule Kinase Inhibitor Drugs (1995–2021): Medical Indication, Pharmacology, and Synthesis,” Journal of Medicinal Chemistry 65, no. 2 (2021): 1047–1131.

[208] J. Renukuntla, A. D. Vadlapudi, A. Patel, S. H. Boddu, and A. K. Mitra, “Approaches for Enhancing Oral Bioavailability of Peptides and Proteins,” International Journal of Pharmaceutics 447, no. 1-2 (2013): 75–93.

[209] N. J. Yang and M. J. Hinner, “Getting Across the Cell Membrane: An Overview for Small Molecules, Peptides, and Proteins,” Site-Specific Protein Labeling: Methods and Protocols 1266 (2014): 29–53.

[210] L. Chen, X. Zhao, X. Liu, Y. Ouyang, C. Xu, and Y. Shi, “Development of Small Molecule Drugs Targeting Immune Checkpoints,” Cancer Biology & Medicine 21, no. 5 (2024): 382–399.

[211] A. Osipov, M. T. Saung, L. Zheng, and A. G. Murphy, “Small Molecule Immunomodulation: The Tumor Microenvironment and Overcoming Immune Escape,” Journal for Immunotherapy of Cancer 7 (2019): 1–12.

[212] J. S. Sebolt-Leopold and J. M. English, “Mechanisms of Drug Inhibition of Signalling Molecules,” Nature 441, no. 7092 (2006): 457–462.

[213] Y. Guo, J. Bae, Z. Fang, P. Li, F. Zhao, and G. Yu, “Hydrogels and Hydrogel-derived Materials for Energy and Water Sustainability,” Chemical Reviews 120, no. 15 (2020): 7642–7707.

[214] J. Li and D. J. Mooney, “Designing Hydrogels for Controlled Drug Delivery,” Nature Reviews Materials 1, no. 12 (2016): 1–17.

[215] G. Curigliano, E. L. Mayer, H. J. Burstein, E. P. Winer, and A. Goldhirsch, “Cardiac Toxicity From Systemic Cancer Therapy: A Comprehensive Review,” Progress in Cardiovascular Diseases 53, no. 2 (2010): 94–104.

[216] S. Mazzaferro, K. Bouchemal, and G. Ponchel, “Oral Delivery of Anticancer Drugs I: General Considerations,” Drug Discovery Today 18, no. 1-2 (2013): 25–34.

[217] E. Senkus and J. Jassem, “Cardiovascular Effects of Systemic Cancer Treatment,” Cancer Treatment Reviews 37, no. 4 (2011): 300–311.

[218] C. S. Kue, A. Kamkaew, K. Burgess, L. V. Kiew, L. Y. Chung, and H. B. Lee, “Small Molecules for Active Targeting in Cancer,” Medicinal Research Reviews 36, no. 3 (2016): 494–575.

[219] C. Widakowich, G. de Castro, E. De Azambuja, P. Dinh, and A. Awada, “Side Effects of Approved Molecular Targeted Therapies in Solid Cancers,” The Oncologist 12, no. 12 (2007): 1443–1455.

[220] R. Narayanaswamy and V. P. Torchilin, “Hydrogels and Their Applications in Targeted Drug Delivery,” Molecules (Basel, Switzerland) 24, no. 3 (2019): 603.

[221] Y. Ke, K. Xin, Y. Tao, et al., “A Thermosensitive Bi-Adjuvant Hydrogel Triggers Epitope Spreading to Promote the Anti-Tumor Efficacy of Frameshift Neoantigens,” Advanced Science (Weinheim) 11, no. 14 (2024): e2306889.

[222] D. V. Krysko, A. D. Garg, A. Kaczmarek, O. Krysko, P. Agostinis, and P. Vandenabeele, “Immunogenic Cell Death and DAMPs in Cancer Therapy,” Nature Reviews Cancer 12, no. 12 (2012): 860–875.

[223] J. Li, G. Luo, C. Zhang, et al., “In Situ Injectable Hydrogel-loaded Drugs Induce Anti-tumor Immune Responses in Melanoma Immunochemotherapy,” Materials Today Bio 14 (2022): 100238.

[224] B. Wu, J. Liang, X. Yang, et al., “A Programmable Peptidic Hydrogel Adjuvant for Personalized Immunotherapy in Resected Stage Tumors,” Journal of the American Chemical Society 146, no. 12 (2024): 8585–8597.

[225] T. Xiao, J. Zhu, L. Jia, et al., “Injectable Alginate Hydrogels for Synergistic Tumor Combination Therapy Through Repolarization of Tumor-associated Macrophages,” Journal of Controlled Release 348 (2022): 239–249.

[226] A. Kumar, S. K. Sahoo, K. Padhee, P. S. Kochar, A. Sathapathy, and N. Pathak, “Review on Solubility Enhancement Techniques for Hydrophobic Drugs,” Pharmacie Globale 3, no. 3 (2011): 001–007.

[227] E. M. Ahmed, “Hydrogel: Preparation, Characterization, and Applications: A Review,” Journal of Advanced Research 6, no. 2 (2015): 105–121.

[228] E. Larrañeta, S. Stewart, M. Ervine, R. Al-Kasasbeh, and R. F. Donnelly, “Hydrogels for Hydrophobic Drug Delivery. Classification, Synthesis and Applications,” Journal of Functional Biomaterials 9, no. 1 (2018): 13.

[229] S. Shumack, J. Robinson, S. Kossard, et al., “Efficacy of Topical 5% Imiquimod Cream for the Treatment of Nodular Basal Cell Carcinoma: Comparison of Dosing Regimens,” Archives of Dermatology 138, no. 9 (2002): 1165–1171.

[230] D. Cao, W. Guo, C. Cai, et al., “Unified Therapeutic-Prophylactic Vaccine Demonstrated With a Postoperative Filler Gel to Prevent Tumor Recurrence and Metastasis,” Advanced Functional Materials 32, no. 40 (2022): 2206084.

[231] Z. Meng, X. Fang, B. Fu, et al., “Tumor Immunotherapy Boosted by R837 Nanocrystals Through Combining Chemotherapy and Mild Hyperthermia,” Journal of Controlled Release 350 (2022): 841–856.

[232] Y. Yin, X. Li, H. Ma, et al., “In Situ Transforming RNA Nanovaccines From Polyethylenimine Functionalized Graphene Oxide Hydrogel for Durable Cancer Immunotherapy,” Nano Letters 21, no. 5 (2021): 2224–2231.

[233] J. A. Kemp, M. S. Shim, C. Y. Heo, and Y. J. Kwon, “Combo″ Nanomedicine: Co-delivery of Multi-modal Therapeutics for Efficient, Targeted, and Safe Cancer Therapy,” Advanced Drug Delivery Reviews 98 (2016): 3–18.

[234] J. Q. Zhu, H. Wu, Z. L. Li, et al., “Responsive Hydrogels Based on Triggered Click Reactions for Liver Cancer,” Advanced Materials 34, no. 38 (2022): 2201651.

[235] M. Wang, Q. Hu, J. Huang, et al., “In Situ Formed ROS-Responsive Hydrogel With STING Agonist and Gemcitabine to Intensify Immunotherapy Against Pancreatic Ductal Adenocarcinoma,” Advanced Healthcare Materials 12, no. 20 (2023): e2203264.

[236] S. Crunkhorn, “New Path to Improving Immunotherapy,” Nature Reviews Drug Discovery 17, no. 3 (2018): 164–164.

[237] E. Lim, E. P. Hamilton, R. Redman, et al., “Abstract CT146: RGX-104, a First-in-class Immunotherapy Targeting the Liver-X Receptor (LXR): Initial Results From the Phase 1b RGX-104 plus docetaxel Combination Dose Escalation Cohorts,” Cancer Research 80, no. 16_Supplement (2020): CT146–CT146.

[238] X. Li, X. Liang, W. Fu, et al., “Reversing Cancer Immunoediting Phases With a Tumor-activated and Optically Reinforced Immunoscaffold,” Bioactive Materials 35 (2024): 228–241.

[239] K. Jomova, M. Makova, S. Y. Alomar, et al., “Essential Metals in Health and Disease,” Chemico-Biological Interactions 367 (2022): 110173.

[240] L. Zhao, Y. Gui, J. Cai, and X. Deng, “Biometallic Ions and Derivatives: A New Direction for Cancer Immunotherapy,” Molecular Cancer 24, no. 1 (2025): 17.

[241] P. Ginefra, H. Carrasco Hope, M. Spagna, A. Zecchillo, and N. Vannini, “Ionic Regulation of T-cell Function and Anti-tumour Immunity,” International Journal of Molecular Sciences 22, no. 24 (2021): 13668.

[242] K. Yuan, C. Zhang, X. Pan, B. Hu, J. Zhang, and G. Yang, “Immunomodulatory Metal-based Biomaterials for Cancer Immunotherapy,” Journal of Controlled Release 375 (2024): 249–268.

[243] S. Qin, Y. Niu, Y. Zhang, et al., “Metal Ion-containing Hydrogels: Synthesis, Properties, and Applications in Bone Tissue Engineering,” Biomacromolecules 25, no. 6 (2024): 3217–3248.

[244] C. Su, D. Lin, X. Huang, et al., “Developing Hydrogels for Gene Therapy and Tissue Engineering,” Journal of Nanobiotechnology 22, no. 1 (2024): 182.

[245] H. Cao, L. Duan, Y. Zhang, J. Cao, and K. Zhang, “Current Hydrogel Advances in Physicochemical and Biological Response-driven Biomedical Application Diversity,” Signal Transduction and Targeted Therapy 6, no. 1 (2021): 426.

[246] Y. You, Z. Guo, T. Wolter, and Q. Hu, “Intracellular Metal Ion-based Chemistry for Programmed Cell Death,” Chemical Society Reviews 54, no. 3 (2025): 1552–1582.

[247] K. Peters, S. Staehlke, H. Rebl, A. Jonitz-Heincke, and O. Hahn, “Impact of Metal Ions on Cellular Functions: A Focus on Mesenchymal Stem/Stromal Cell Differentiation,” International Journal of Molecular Sciences 25, no. 18 (2024): 10127.

[248] M. Jia, X. Zhou, P. Li, and S. Zhang, “An Injectable Biomimetic Hydrogel Adapting Brain Tissue Mechanical Strength for Postoperative Treatment of Glioblastoma Without Anti-tumor Drugs Participation,” Journal of Controlled Release 373 (2024): 699–712.

[249] B. Liu and K. Chen, “Advances in Hydrogel-based Drug Delivery Systems,” Gels 10, no. 4 (2024): 262.

[250] A. C. Marques, P. J. Costa, S. Velho, and M. H. Amaral, “Stimuli-responsive Hydrogels for Intratumoral Drug Delivery,” Drug Discovery Today 26, no. 10 (2021): 2397–2405.

[251] F. Chen, H. Li, C. Zhen, et al., “Intelligent Sensing Switches in Drug Delivery Systems: Mechanisms, Material Selection, and Future Perspectives,” Journal of Biomedical Materials Research Part A 113, no. 6 (2025): e37938.

[252] J. Wang, B. Li, R. C. Cooper, D. Huang, and H. Yang, “Localized Sustained Release of Copper Enhances Antitumor Effects of Disulfiram in Head and Neck Cancer,” Biomacromolecules 25, no. 5 (2024): 2770–2779.

[253] Y. Hu, W. Yang, J. Zhan, C. Pu, L. Zhong, and H. Hou, “Eutectogels: Recent Advances and Emerging Biological Applications,” Advanced Functional Materials 35 (2025): 2425778.

[254] A. M. Curreri, S. Mitragotri, and E. E. Tanner, “Recent Advances in Ionic Liquids in Biomedicine,” Advanced Science 8, no. 17 (2021): 2004819.

[255] K. O. Margossian, M. U. Brown, T. Emrick, and M. Muthukumar, “Coacervation in Polyzwitterion-polyelectrolyte Systems and Their Potential Applications for Gastrointestinal Drug Delivery Platforms,” Nature Communications 13, no. 1 (2022): 2250.

[256] X. Wang, C. Li, Y. Wang, et al., “Smart Drug Delivery Systems for Precise Cancer Therapy,” Acta Pharmaceutica Sinica B 12, no. 11 (2022): 4098–4121.

[257] B. Tian and J. Liu, “Smart Stimuli-responsive chitosan Hydrogel for Drug Delivery: A Review,” International Journal of Biological Macromolecules 235 (2023): 123902.

[258] P. Tordi, F. Ridi, P. Samorì, and M. Bonini, “Cation-Alginate Complexes and Their Hydrogels: A Powerful Toolkit for the Development of Next-Generation Sustainable Functional Materials,” Advanced Functional Materials 35, no. 9 (2025): 2416390.

[259] E. J. Delgado-Pujol, G. Martínez, D. Casado-Jurado, et al., “Hydrogels and Nanogels: Pioneering the Future of Advanced Drug Delivery Systems,” Pharmaceutics 17, no. 2 (2025): 215.

[260] Y. Sun, L.-G. Chen, X.-M. Fan, and J.-L. Pang, “Ultrasound Responsive Smart Implantable Hydrogels for Targeted Delivery of Drugs: Reviewing Current Practices,” International Journal of Nanomedicine 17 (2022): 5001.

[261] Y. Zhu, Z. Yang, Z. Pan, et al., “Metallo-alginate Hydrogel Can Potentiate Microwave Tumor Ablation for Synergistic Cancer Treatment,” Science Advances 8, no. 31 (2022): eabo5285.

[262] Y. Li, Z. Zhu, S. Hua, et al., “Metal-based Nanoparticles Promote the Activation of cGAS-STING Pathway for Enhanced Cancer Immunotherapy,” Nano Today 58 (2024): 102445.

[263] S. Bera, H. K. Datta, and P. Dastidar, “An Injectable Supramolecular Hydrogel as a Self-drug-delivery System for Local Chemoimmunotherapy Against Melanoma,” Biomaterials Science 11, no. 16 (2023): 5618–5633.

[264] X. K. Jin, J. L. Liang, S. M. Zhang, et al., “Engineering Metal-based Hydrogel-mediated Tertiary Lymphoid Structure Formation via Activation of the STING Pathway for Enhanced Immunotherapy,” Materials Horizons 10, no. 10 (2023): 4365–4379.

[265] S. Hager, F. J. Fittler, E. Wagner, and M. Bros, “Nucleic Acid-based Approaches for Tumor Therapy,” Cells 9, no. 9 (2020): 2061.

[266] Y. Wang and F. Yuan, “Delivery of Viral Vectors to Tumor Cells: Extracellular Transport, Systemic Distribution, and Strategies for Improvement,” Annals of Biomedical Engineering 34 (2006): 114–127.

[267] N. K. Green and L. W. Seymour, “Adenoviral Vectors: Systemic Delivery and Tumor Targeting,” Cancer Gene Therapy 9, no. 12 (2002): 1036–1042.

[268] J. Li, Y. Wang, Y. Zhu, and D. Oupický, “Recent Advances in Delivery of Drug–nucleic Acid Combinations for Cancer Treatment,” Journal of Controlled Release 172, no. 2 (2013): 589–600.

[269] A. Schambach, D. Zychlinski, B. Ehrnstroem, and C. Baum, “Biosafety Features of Lentiviral Vectors,” Human Gene Therapy 24, no. 2 (2013): 132–142.

[270] C. Papayannakos and R. Daniel, “Understanding Lentiviral Vector Chromatin Targeting: Working to Reduce Insertional Mutagenic Potential for Gene Therapy,” Gene Therapy 20, no. 6 (2013): 581–588.

[271] S. Wilhelm, A. J. Tavares, Q. Dai, et al., “Analysis of Nanoparticle Delivery to Tumours,” Nature Reviews Materials 1, no. 5 (2016): 1–12.

[272] R. Cai and C. Chen, “The Crown and the Scepter: Roles of the Protein Corona in Nanomedicine,” Advanced Materials 31, no. 45 (2019): 1805740.

[273] S. Xu, J. Cai, H. Cheng, and W. Wang, “Sustained Release of Therapeutic Gene by Injectable Hydrogel for Hepatocellular Carcinoma,” International Journal of Pharmaceutics: X 6 (2023): 100195.

[274] J. Song, H. Zhang, D. Wang, et al., “Hydrogel Loading Functionalized PAMAM/shRNA Complex for Postsurgical Glioblastoma Treatment,” Journal of Control Release 338 (2021): 583–592.

[275] S. Mikkola, T. Lönnberg, and H. Lönnberg, “Phosphodiester Models for Cleavage of Nucleic Acids,” Beilstein Journal of Organic Chemistry 14, no. 1 (2018): 803–837.

[276] F. Jia, W. Huang, Y. Yin, et al., “Stabilizing RNA Nanovaccines With Transformable Hyaluronan Dynamic Hydrogel for Durable Cancer Immunotherapy,” Advanced Functional Materials 33, no. 3 (2022): 2204636.

[277] K. C. Nitiss, A. Bandak, J. M. Berger, and J. L. Nitiss, “Genome Instability Induced by Topoisomerase Misfunction,” International Journal of Molecular Sciences 25, no. 19 (2024): 10247.

[278] K. Kawane, K. Motani, and S. Nagata, “DNA Degradation and Its Defects,” Cold Spring Harbor Perspectives in Biology 6, no. 6 (2014): a016394.

[279] H. Zhang, J. Vandesompele, K. Braeckmans, S. C. De Smedt, and K. Remaut, “Nucleic Acid Degradation as Barrier to Gene Delivery: A Guide to Understand and Overcome Nuclease Activity,” Chemical Society Reviews 53, no. 1 (2024): 317–360.

[280] G. Zhou, Q. Zhou, R. Li, et al., “Synthetically Engineered Bacterial Extracellular Vesicles and IL-4-Encapsulated Hydrogels Sequentially Promote Osteoporotic Fracture Repair,” ACS Nano 19, no. 16 (2025): 16064–16083.

[281] B. Zhao, B. Zhou, K. Shi, et al., “Sustained and Targeted Delivery of siRNA/DP7-C Nanoparticles From Injectable Thermosensitive Hydrogel for Hepatocellular Carcinoma Therapy,” Cancer Science 112, no. 6 (2021): 2481–2492.

[282] M. Lu, H. Xing, A. Zheng, Y. Huang, and X.-J. Liang, “Overcoming Pharmaceutical Bottlenecks for Nucleic Acid Drug Development,” Accounts of Chemical Research 56, no. 3 (2023): 224–236.

[283] L. Urban, M. Maciejewski, E. Lounkine, et al., “Translation of off-target Effects: Prediction of ADRs by Integrated Experimental and Computational Approach,” Toxicology Research 3, no. 6 (2014): 433–444.

[284] A. Fakhari and J. A. Subramony, “Engineered in-situ Depot-forming Hydrogels for Intratumoral Drug Delivery,” Journal of Controlled Release 220 (2015): 465–475.

[285] E. A. Chiocca and S. D. Rabkin, “Oncolytic Viruses and Their Application to Cancer Immunotherapy,” Cancer Immunology Research 2, no. 4 (2014): 295–300.

[286] J.-W. Choi, Y. S. Lee, C.-O. Yun, and S. W. Kim, “Polymeric Oncolytic adenovirus for Cancer Gene Therapy,” Journal of Controlled Release 219 (2015): 181–191.

[287] K. A. Whitehead, R. Langer, and D. G. Anderson, “Knocking Down Barriers: Advances in siRNA Delivery,” Nature Reviews Drug Discovery 8, no. 2 (2009): 129–138.

[288] J. Lu, J. Song, P. Zhang, et al., “Biomineralized Polydopamine Nanoparticle-Based Sodium Alginate Hydrogels for Delivery of Anti-Serine/Threonine Protein Kinase B-Rapidly Accelerated Fibrosarcoma siRNA for Metastatic Melanoma Therapy,” ACS Nano 17, no. 18 (2023): 18318–18331.

[289] S. Kulanayake and S. K. Tikoo, “Adenovirus Core Proteins: Structure and Function,” Viruses 13, no. 3 (2021): 388.

[290] I. Nadeau and A. Kamen, “Production of adenovirus Vector for Gene Therapy,” Biotechnology Advances 20, no. 7-8 (2003): 475–489.

[291] B. Thaci, I. V. Ulasov, D. A. Wainwright, and M. S. Lesniak, “The Challenge for Gene Therapy: Innate Immune Response to Adenoviruses,” Oncotarget 2, no. 3 (2011): 113.

[292] P. Lv, H. Chen, H. Cheng, et al., “A Calcium Alginate Hydrogel Microsphere-Based Transcatheter Arterial Viroembolization Strategy for Hepatocellular Carcinoma,” Advanced Therapeutics 6, no. 4 (2023): 2200174.

[293] B. Zheng, W. Peng, L. Gan, et al., “Sendai Virus-based Immunoadjuvant in Hydrogel Vaccine Intensity-modulated Dendritic Cells Activation for Suppressing Tumorigenesis,” Bioactive Materials 6, no. 11 (2021): 3879–3891.

[294] M. Wu, H. Li, C. Zhang, et al., “Silk-Gel Powered Adenoviral Vector Enables Robust Genome Editing of PD-L1 to Augment Immunotherapy Across Multiple Tumor Models,” Advanced Science (Weinheim) 10, no. 12 (2023): e2206399.

[295] N. K. Wolf, D. U. Kissiov, and D. H. Raulet, “Roles of Natural Killer Cells in Immunity to Cancer, and Applications to Immunotherapy,” Nature Reviews Immunology 23, no. 2 (2023): 90–105.

[296] A. Helmin-Basa, L. Gackowska, S. Balcerowska, M. Ornawka, N. Naruszewicz, and M. Wiese-Szadkowska, “The Application of the Natural Killer Cells, Macrophages and Dendritic Cells in Treating Various Types of Cancer,” Physical Sciences Reviews 7, no. 8 (2022): 833–866.

[297] E. Blass and P. A. Ott, “Advances in the Development of Personalized Neoantigen-based Therapeutic Cancer Vaccines,” Nature Reviews Clinical Oncology 18, no. 4 (2021): 215–229.

[298] A. S. Mikhail, R. Morhard, M. Mauda-Havakuk, M. Kassin, A. Arrichiello, and B. J. Wood, “Hydrogel Drug Delivery Systems for Minimally Invasive Local Immunotherapy of Cancer,” Advanced Drug Delivery Reviews 202 (2023): 115083.

[299] B. Zhang, Y. Su, J. Zhou, Y. Zheng, and D. Zhu, “Toward a Better Regeneration Through Implant-mediated Immunomodulation: Harnessing the Immune Responses,” Advanced Science 8, no. 16 (2021): 2100446.

[300] B. S. Ou, O. M. Saouaf, J. Baillet, and E. A. Appel, “Sustained Delivery Approaches to Improving Adaptive Immune Responses,” Advanced Drug Delivery Reviews 187 (2022): 114401.

[301] Y. Ding, Y. Wang, and Q. Hu, Recent Advances in Overcoming Barriers to Cell-based Delivery Systems for Cancer Immunotherapy (Wiley Online Library, 2022): 20210106.

[302] Z. Li, Y. Wang, Y. Ding, L. Repp, G. S. Kwon, and Q. Hu, “Cell-based Delivery Systems: Emerging Carriers for Immunotherapy,” Advanced Functional Materials 31, no. 23 (2021): 2100088.

[303] S. Hu, C. Zeng, Y. Jiang, W. Kong, and M. Zhu, “Macrostructure and Microenvironment Biomimetic Hydrogel: Design, Properties, and Tissue Engineering Application,” Chemistry of Materials 36, no. 3 (2024): 1054–1087.

[304] F. J. Vernerey, S. Lalitha Sridhar, A. Muralidharan, and S. J. Bryant, “Mechanics of 3D Cell–hydrogel Interactions: Experiments, Models, and Mechanisms,” Chemical Reviews 121, no. 18 (2021): 11085–11148.

[305] Y. Ma, T. Han, Q. Yang, et al., “Viscoelastic Cell Microenvironment: Hydrogel-based Strategy for Recapitulating Dynamic ECM Mechanics,” Advanced Functional Materials 31, no. 24 (2021): 2100848.

[306] J. Jie, D. Mao, J. Cao, P. Feng, and P. Yang, “Customized Multifunctional Peptide Hydrogel Scaffolds for CAR-T-cell Rapid Proliferation and Solid Tumor Immunotherapy,” ACS Applied Materials & Interfaces 14, no. 33 (2022): 37514–37527.

[307] J. D. Chan, J. Lai, C. Y. Slaney, A. Kallies, P. A. Beavis, and P. K. Darcy, “Cellular Networks Controlling T Cell Persistence in Adoptive Cell Therapy,” Nature Reviews Immunology 21, no. 12 (2021): 769–784.

[308] P. Zhang, G. Zhang, and X. Wan, “Challenges and New Technologies in Adoptive Cell Therapy,” Journal of Hematology & Oncology 16, no. 1 (2023): 97.

[309] F. Santos, J. Valderas-Gutiérrez, E. P. Del Río, et al., “Enhanced human T Cell Expansion With Inverse Opal Hydrogels,” Biomaterials Science 10, no. 14 (2022): 3730–3738.

[310] F. Paradiso, S. Serpelloni, L. W. Francis, and F. Taraballi, “Mechanical Studies of the Third Dimension in Cancer: From 2D to 3D Model,” International Journal of Molecular Sciences 22, no. 18 (2021): 10098.

[311] C. Wang, R. R. Varshney, and D.-A. Wang, “Therapeutic Cell Delivery and Fate Control in Hydrogels and Hydrogel Hybrids,” Advanced Drug Delivery Reviews 62, no. 7-8 (2010): 699–710.

[312] D. A. Foyt, M. D. Norman, T. T. Yu, and E. Gentleman, “Exploiting Advanced Hydrogel Technologies to Address Key Challenges in Regenerative Medicine,” Advanced Healthcare Materials 7, no. 8 (2018): 1700939.

[313] Z. Yang, Q. Shen, L. Xing, et al., “A Biophotonic Device Based on a Conjugated Polymer and a Macrophage-laden Hydrogel for Triggering Immunotherapy,” Materials Horizons 10, no. 6 (2023): 2226–2236.

[314] X. Lei, Y. Lei, J.-K. Li, et al., “Immune Cells Within the Tumor Microenvironment: Biological Functions and Roles in Cancer Immunotherapy,” Cancer Letters 470 (2020): 126–133.

[315] D. J. Irvine, M. V. Maus, D. J. Mooney, and W. W. Wong, “The Future of Engineered Immune Cell Therapies,” Science 378, no. 6622 (2022): 853–858.

[316] C. Bordignon, C. Carlo-Stella, M. P. Colombo, et al., “Cell Therapy: Achievements and Perspectives,” Haematologica 84, no. 12 (1999): 1110–1149.

[317] Q. Ding, Z. Wu, K. Tao, et al., “Environment Tolerant, Adaptable and Stretchable Organohydrogels: Preparation, Optimization, and Applications,” Materials Horizons 9, no. 5 (2022): 1356–1386.

[318] Z. Liu, Z. Zhou, Q. Dang, et al., “Immunosuppression in Tumor Immune Microenvironment and Its Optimization From CAR-T Cell Therapy,” Theranostics 12, no. 14 (2022): 6273.

[319] Q. Hu, H. Li, E. Archibong, et al., “Inhibition of Post-surgery Tumour Recurrence via a Hydrogel Releasing CAR-T Cells and Anti-PDL1-conjugated Platelets,” Nature Biomedical Engineering 5, no. 9 (2021): 1038–1047.

[320] A. J. Hou, L. C. Chen, and Y. Y. Chen, “Navigating CAR-T Cells Through the Solid-tumour Microenvironment,” Nature Reviews Drug Discovery 20, no. 7 (2021): 531–550.

[321] A. Cheever, M. Townsend, and K. O'Neill, “Tumor Microenvironment Immunosuppression: A Roadblock to CAR T-cell Advancement in Solid Tumors,” Cells 11, no. 22 (2022): 3626.

[322] M. Martinez and E. K. Moon, “CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment,” Frontiers in Immunology 10 (2019): 128.

[323] W. Zhou, S. Lei, M. Liu, et al., “Injectable and Photocurable CAR-T Cell Formulation Enhances the Anti-tumor Activity to Melanoma in Mice,” Biomaterials 291 (2022): 121872.

[324] E. Scibona and M. Morbidelli, “Expansion Processes for Cell-based Therapies,” Biotechnology Advances 37, no. 8 (2019): 107455.

[325] C. J. Bashor, I. B. Hilton, H. Bandukwala, D. M. Smith, and O. Veiseh, “Engineering the next Generation of Cell-based Therapeutics,” Nature Reviews Drug Discovery 21, no. 9 (2022): 655–675.

[326] A. Kaiser, M. Assenmacher, B. Schröder, et al., “Towards a Commercial Process for the Manufacture of Genetically Modified T Cells for Therapy,” Cancer Gene Therapy 22, no. 2 (2015): 72–78.

[327] J. Stoops, T. Morton, J. Powell, A. L. Pace, and J. A. Bluestone, “Treg Cell Therapy Manufacturability: Current state of the Art, Challenges and New Opportunities,” Frontiers in Immunology 16 (2025): 1604483.

[328] L. Diao and M. Liu, “Rethinking Antigen Source: Cancer Vaccines Based on Whole Tumor Cell/Tissue Lysate or Whole Tumor Cell,” Advanced Science 10, no. 22 (2023): 2300121.

[329] C. L.-L. Chiang, F. Benencia, and G. Coukos, Whole Tumor Antigen Vaccines (Elsevier, 2010): 132–143.

[330] Y. Zhou, Y. Wei, X. Tian, and X. Wei, “Cancer Vaccines: Current Status and Future Directions,” Journal of Hematology & Oncology 18, no. 1 (2025): 18.

[331] J. Liu, S. S. Liew, J. Wang, and K. Pu, “Bioinspired and Biomimetic Delivery Platforms for Cancer Vaccines,” Advanced Materials 34, no. 1 (2022): 2103790.

[332] S. Ruan, Y. Huang, M. He, and H. Gao, “Advanced Biomaterials for Cell-specific Modulation and Restore of Cancer Immunotherapy,” Advanced Science 9, no. 16 (2022): 2200027.

[333] T. He, Y. Shi, X. Kou, et al., “Antigenicity and Adjuvanticity co-reinforced Personalized Cell Vaccines Based on Self-adjuvanted Hydrogel for Post-surgical Cancer Vaccination,” Biomaterials 301 (2023): 122218.

[334] Z. Zhang, M. Lu, Y. Qin, et al., “Neoantigen: A New Breakthrough in Tumor Immunotherapy,” Frontiers in Immunology 12 (2021): 672356.

[335] X. Li, J. You, L. Hong, W. Liu, P. Guo, and X. Hao, “Neoantigen Cancer Vaccines: A New Star on the Horizon,” Cancer Biology & Medicine 21, no. 4 (2024): 274–311.

[336] Z. Liu, J. Lv, Q. Dang, et al., “Engineering Neoantigen Vaccines to Improve Cancer Personalized Immunotherapy,” International Journal of Biological Sciences 18, no. 15 (2022): 5607.

[337] L. Kraehenbuehl, C.-H. Weng, S. Eghbali, J. D. Wolchok, and T. Merghoub, “Enhancing Immunotherapy in Cancer by Targeting Emerging Immunomodulatory Pathways,” Nature Reviews Clinical Oncology 19, no. 1 (2022): 37–50.

[338] S. Han and J. Wu, “Three-dimensional (3D) Scaffolds as Powerful Weapons for Tumor Immunotherapy,” Bioactive Materials 17 (2022): 300–319.

[339] J. Mondal, K. Chakraborty, E. J. Bunggulawa, et al., “Recent Advancements of Hydrogels in Immunotherapy: Breast Cancer Treatment,” Journal of Controlled Release 372 (2024): 1–30.

[340] G. A. Roth, V. C. Picece, B. S. Ou, W. Luo, B. Pulendran, and E. A. Appel, “Designing Spatial and Temporal Control of Vaccine Responses,” Nature Reviews Materials 7, no. 3 (2022): 174–195.

[341] L. Mao, P. Ma, X. Luo, et al., “Stimuli-responsive Polymeric Nanovaccines Toward next-generation Immunotherapy,” ACS Nano 17, no. 11 (2023): 9826–9849.

[342] A. Roy, K. Manna, and S. Pal, “Recent Advances in Various Stimuli-responsive Hydrogels: From Synthetic Designs to Emerging Healthcare Applications,” Materials Chemistry Frontiers 6, no. 17 (2022): 2338–2385.

[343] R. Cui, Q. Wu, J. Wang, et al., “Hydrogel-by-design: Smart Delivery System for Cancer Immunotherapy,” Frontiers in Bioengineering and Biotechnology 9 (2021): 723490.

[344] F. Farjadian, S. Mirkiani, P. Ghasemiyeh, et al., “Smart Nanogels as Promising Platform for Delivery of Drug, Gene, and Vaccine; Therapeutic Applications and Active Targeting Mechanism,” European Polymer Journal 219 (2024): 113400.

[345] Y. Yoshizaki, K. Horii, N. Murase, A. Kuzuya, and Y. Ohya, “Development of Immune Cell Delivery System Using Biodegradable Injectable Polymers for Cancer Immunotherapy,” International Journal of Pharmaceutics 652 (2024): 123801.

[346] M. L. Marco, M. E. Sanders, M. Gänzle, et al., “The International Scientific Association for Probiotics and Prebiotics (ISAPP) Consensus Statement on Fermented Foods,” Nature Reviews Gastroenterology & Hepatology 18, no. 3 (2021): 196–208.

[347] Y. Ge, X. Wang, Y. Guo, et al., “Gut Microbiota Influence Tumor Development and Alter Interactions With the human Immune System,” Journal of Experimental & Clinical Cancer Research 40 (2021): 1–9.

[348] D. B. Graham and R. J. Xavier, “Conditioning of the Immune System by the Microbiome,” Trends in Immunology 44, no. 7 (2023): 499–511.

[349] M. Yang, F. Yang, W. Chen, S. Liu, L. Qiu, and J. Chen, “Bacteria-mediated Cancer Therapies: Opportunities and Challenges,” Biomaterials Science 9, no. 17 (2021): 5732–5744.

[350] X. Liu, M. E. Inda, Y. Lai, T. K. Lu, and X. Zhao, “Engineered Living Hydrogels,” Advanced Materials 34, no. 26 (2022): 2201326.

[351] Z. Li, Y. Wang, J. Liu, et al., “Chemically and Biologically Engineered Bacteria-based Delivery Systems for Emerging Diagnosis and Advanced Therapy,” Advanced Materials 33, no. 38 (2021): 2102580.

[352] X. Hu, L. Zhang, L. Yan, and L. Tang, “Recent Advances in Polysaccharide-based Physical Hydrogels and Their Potential Applications for Biomedical and Wastewater Treatment,” Macromolecular Bioscience 22, no. 9 (2022): 2200153.

[353] K. Quan, J. Hou, Z. Zhang, et al., “Water in Bacterial Biofilms: Pores and Channels, Storage and Transport Functions,” Critical Reviews in Microbiology 48, no. 3 (2022): 283–302.

[354] S. Yu, H. Sun, Y. Li, S. Wei, J. Xu, and J. Liu, “Hydrogels as Promising Platforms for Engineered Living Bacteria-mediated Therapeutic Systems,” Materials Today Bio 16 (2022): 100435.

[355] A. Mukherjee, B. N. Singh, S. Kaur, et al., “Unearthing the Power of Microbes as Plant Microbiome for Sustainable Agriculture,” Microbiological Research 286 (2024): 127780.

[356] W. M. De Vos, H. Tilg, M. Van Hul, and P. D. Cani, “Gut Microbiome and Health: Mechanistic Insights,” Gut 71, no. 5 (2022): 1020–1032.

[357] X. Pan, F. Liu, R. Kang, et al., “Self-Adjuvanting Bacteria Hydrogel for SHP1 Checkpoint Inhibition in Tumor-Draining Lymph Nodes to Enhance Cancer Immunotherapy,” Advanced Functional Materials 34, no. 51 (2024): 2409736.

[358] L. Huang, Z. Guo, X. Yang, et al., “Advancements in GelMA Bioactive Hydrogels: Strategies for Infection Control and Bone Tissue Regeneration,” Theranostics 15, no. 2 (2025): 460.

[359] D.-W. Zheng, W.-W. Deng, W.-F. Song, et al., “Biomaterial-mediated Modulation of Oral Microbiota Synergizes With PD-1 Blockade in Mice With Oral Squamous Cell Carcinoma,” Nature Biomedical Engineering 6, no. 1 (2022): 32–43.

[360] Y. Qiu, M. Fan, Y. Wang, et al., “Sulfate-reducing Bacteria Loaded in Hydrogel as a Long-lasting H2S Factory for Tumor Therapy,” Journal of Controlled Release 360 (2023): 647–659.

[361] S.-Y. Kwon, H. Thi-Thu Ngo, J. Son, Y. Hong, and J.-J. Min, “Exploiting Bacteria for Cancer Immunotherapy,” Nature Reviews Clinical Oncology 21, no. 8 (2024): 569–589.

[362] D. Zhu, W. Pan, H. Li, J. Hua, C. Zhang, and K. Zhao, “Innovative Applications of Bacteria and Their Derivatives in Targeted Tumor Therapy,” ACS Nano 19, no. 5 (2025): 5077–5109.

[363] K. S. Allemailem, “Innovative Approaches of Engineering Tumor-targeting Bacteria With Different Therapeutic Payloads to Fight Cancer: A Smart Strategy of Disease Management,” International Journal of Nanomedicine 16 (2021): 8159–8184.

[364] M. Ijaz, I. Hasan, T. H. Chaudhry, et al., “Bacterial Derivatives Mediated Drug Delivery in Cancer Therapy: A New Generation Strategy,” Journal of Nanobiotechnology 22, no. 1 (2024): 510.

[365] S. Bhusari, J. Kim, K. Polizzi, S. Sankaran, and A. Del Campo, “Encapsulation of Bacteria in Bilayer Pluronic Thin Film Hydrogels: A Safe Format for Engineered Living Materials,” Biomaterials Advances 145 (2023): 213240.

[366] X. Meng, Z. Liu, Y. Yang, et al., “Engineered Microcystis Aerugiosa Hydrogel as an Anti-Tumor Therapeutic by Augmenting Tumor Immunogenicity and Immune Responses,” Advanced Functional Materials 34, no. 7 (2024): 2305915.

[367] L. Zhu, J. Liu, M. Qiu, et al., “Bacteria-mediated Metformin-loaded Peptide Hydrogel Reprograms the Tumor Immune Microenvironment in Glioblastoma,” Biomaterials 288 (2022): 121711.

[368] A. Chen, J. Zhu, R. Liu, et al., “Injectable Thermo-sensitive Hydrogel Enhances Anti-tumor Potency of Engineered Lactococcus Lactis by Activating Dendritic Cells and Effective Memory T Cells,” Bioactive Materials 37 (2024): 331–347.

[369] M. Kremenovic, A. A. Chan, B. Feng, et al., “BCG Hydrogel Promotes CTSS-mediated Antigen Processing and Presentation, Thereby Suppressing Metastasis and Prolonging Survival in Melanoma,” Journal for Immunotherapy of Cancer 10, no. 6 (2022): e004133.

[370] G. Patroklou, E. Triantafyllopoulou, P.-E. Goula, et al., “pH-Responsive Hydrogels: Recent Advances in Pharmaceutical Applications,” Polymers 17, no. 11 (2025): 1451.

[371] K. Gao and K. Xu, “Advancements and Prospects of pH-Responsive Hydrogels in Biomedicine,” Gels 11, no. 4 (2025): 293.

[372] S. Liang, L. Xiao, T. Chen, et al., “Injectable Nanocomposite Hydrogels Improve Intraperitoneal co-delivery of Chemotherapeutics and Immune Checkpoint Inhibitors for Enhanced Peritoneal Metastasis Therapy,” ACS Nano 18, no. 29 (2024): 18963–18979.

[373] B. H. Pogostin, S. X. Wu, M. J. Swierczynski, et al., “Nanofibrous Supramolecular Peptide Hydrogels for Controlled Release of Small-molecule Drugs and Biologics,” Nature Nanotechnology (2025): 1–12.

[374] X. Tang, Y. Wen, Z. Zhang, et al., “Codelivery of Anti-PD-L1 and Indocyanine Green by a β-Cyclodextrin-Based Nanogel Carrier System for Cancer-Targeted Photothermal and Immunotherapy,” Biomacromolecules 26, no. 12 (2025): 8345–8357.

[375] P. Sun, X. Jiang, B. Sun, et al., “Electron-acceptor Density Adjustments for Preparation Conjugated Polymers With NIR-II Absorption and Brighter NIR-II Fluorescence and 1064 Nm Active Photothermal/Gas Therapy,” Biomaterials 280 (2022): 121319.

[376] T. Zhang, Y. Pan, M. Suo, et al., “Photothermal-triggered Sulfur Oxide Gas Therapy Augments Type I Photodynamic Therapy for Potentiating Cancer Stem Cell Ablation and Inhibiting Radioresistant Tumor Recurrence,” Advanced Science 10, no. 29 (2023): 2304042.

[377] B. H. Shan and F. G. Wu, “Hydrogel-based Growth Factor Delivery Platforms: Strategies and Recent Advances,” Advanced Materials 36, no. 5 (2024): 2210707.

[378] Y. Zhao, S. Song, J. Zhang, X. Ren, and Y. Zhao, “Hitchhiking Delivery Systems: Therapeutic Hydrogels as Advanced Tools for Immunomodulatory Applications,” Chemical Reviews 125, no. 17 (2025): 8089–8122.

[379] L. Bejarano, M. J. Jordāo, and J. A. Joyce, “Therapeutic Targeting of the Tumor Microenvironment,” Cancer Discovery 11, no. 4 (2021): 933–959.

[380] Y. Li, L. Zhao, and X.-F. Li, “Hypoxia and the Tumor Microenvironment,” Technology in Cancer Research & Treatment 20 (2021): 15330338211036304.

[381] V. Mohammadzadeh, H. Atapour-Mashhad, S. Shahvali, et al., “Hydrogels as Advanced Drug Delivery Platforms for Cancer Immunotherapy: Promising Innovations and Future Outlook,” Journal of Nanobiotechnology 23, no. 1 (2025): 545.

[382] Y. Feng, Q. Tang, B. Wang, et al., “Targeting the Tumor Microenvironment With Biomaterials for Enhanced Immunotherapeutic Efficacy,” Journal of Nanobiotechnology 22, no. 1 (2024): 737.

[383] H. Ma, C. He, and X. Chen, “Injectable Hydrogels as Local Depots at Tumor Sites for Antitumor Immunotherapy and Immune-based Combination Therapy,” Macromolecular Bioscience 21, no. 6 (2021): 2100039.

[384] J. Han, R. Bhatta, Y. Liu, Y. Bo, and H. Wang, “In Situ Dendritic Cell Recruitment and T Cell Activation for Cancer Immunotherapy,” Frontiers in Pharmacology 13 (2022): 954955.

[385] M.-R. Zhang, L.-L. Fang, Y. Guo, et al., “Advancements in Stimulus-responsive co-delivery Nanocarriers for Enhanced Cancer Immunotherapy,” International Journal of Nanomedicine 19 (2024): 3387–3404.

[386] K. Zhang, K. Xue, and X. J. Loh, “Thermo-responsive Hydrogels: From Recent Progress to Biomedical Applications,” Gels 7, no. 3 (2021): 77.

[387] A. Yaramiri, R. A. Asalh, M. A. Asalh, N. AlSawaftah, W. H. Abuwatfa, and G. A. Husseini, “A Comprehensive Review of Smart Thermosensitive Nanocarriers for Precision Cancer Therapy,” International Journal of Molecular Sciences 26, no. 15 (2025): 7322.

[388] B. Friedman, Y. Dekel, A. Tubaro, et al., “The Chemoablative Effect of Vesigel Instillation in Patients With Nmibc–Preliminary Results: PD11-05,” Journal of Urology 195, no. 4 (2016): e289–e290.

[389] A. Lenis, K. Chamie, B. Friedman, et al., “The Chemoablative Effect of Vesigel Instillation in Patients With Nmibc–Response Rate and 1-Year Durability: PD19-10,” Journal of Urology 197, no. 4 (2017): e368–e369.

[390] S. M. Prasad, D. Shishkov, N. V. Mihaylov, et al., “Primary Chemoablation of Recurrent Low-grade Intermediate-risk Nonmuscle-invasive Bladder Cancer With UGN-102: A Single-arm, Open-label, Phase 3 Trial (ENVISION),” Journal of Urology 213, no. 2 (2024): 205–216.

[391] S. M. Prasad, D. Shishkov, N. Vmihaylov, et al., “PD12-01 Treatment of Recurrent Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer with Ugn-102: Ongoing Results from a Single-Arm, Open-Label, Phase 3 Trial (ENVISION),” Journal of Urology 213, no. 5S (2025): e387.

[392] M. Filon and B. Schmidt, “New Treatment Options for Non–Muscle-Invasive Bladder Cancer,” American Society of Clinical Oncology Educational Book 45, no. 2 (2025): e471942.

[393] D. J. Head and J. D. Raman, “An Evaluation of Mitomycin-containing Reverse Thermal Gel for the Treatment of Low-grade Upper Tract Urothelial Carcinoma,” Expert Review of Anticancer Therapy 24, no. 10 (2024): 943–948.

[394] E. Askari, A. Seyfoori, M. Amereh, et al., “Stimuli-responsive Hydrogels for Local Post-surgical Drug Delivery,” Gels 6, no. 2 (2020): 14.

[395] F. Andrade, E. Durán-Lara, and D. Rafael, Multicomponent Hydrogels for Cancer Diagnosis and Therapy (2023).

[396] Y. Liu, F. Liu, Y. Zeng, et al., “Hydrogel Systems for Spatiotemporal Controlled Delivery of Immunomodulators: Engineering the Tumor Immune Microenvironment for Enhanced Cancer Immunotherapy,” Frontiers in Cell and Developmental Biology 12 (2024): 1514595.

[397] Z. A. Hannouneh, A. Hijazi, A. A. Alsaleem, et al., “Novel Immunotherapeutic Options for BCG-unresponsive High-risk Non-muscle-invasive Bladder Cancer,” Cancer Medicine 12, no. 24 (2023): 21944–21968.

[398] K. Fuchs, R. Duran, A. Denys, P. E. Bize, G. Borchard, and O. Jordan, “Drug-eluting Embolic Microspheres for Local Drug Delivery–State of the Art,” Journal of Controlled Release 262 (2017): 127–138.

[399] A. S. Mikhail, A. H. Negussie, M. Mauda-Havakuk, et al., “Drug-eluting Embolic Microspheres: State-of-the-art and Emerging Clinical Applications,” Expert Opinion on Drug Delivery 18, no. 3 (2021): 383–398.

[400] K. Malagari, M. Pomoni, H. Moschouris, et al., “Chemoembolization of Hepatocellular Carcinoma With HepaSphere 30–60 µm. Safety and Efficacy Study,” Cardiovascular and Interventional Radiology 37, no. 1 (2014): 165–175.

[401] W. Zhang, N. Du, L. Wang, et al., “Effects of HepaSphere Microsphere Encapsule Epirubicin With a New Loading Method Transarterial Chemoembolization: In Vitro and in Vivo Experiments,” Discover Oncology 14, no. 1 (2023): 209.

[402] G. Jia, J. Van Valkenburgh, A. Z. Chen, et al., “Recent Advances and Applications of Microspheres and Nanoparticles in Transarterial Chemoembolization for Hepatocellular Carcinoma,” Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 14, no. 2 (2022): e1749.

[403] N. A. Nuzulia, T. Mart, I. Ahmed, and Y. W. Sari, “The Use of Microspheres for Cancer Embolization Therapy: Recent Advancements and Prospective,” ACS Biomaterials Science & Engineering 10, no. 2 (2024): 637–656.

[404] A. L. Lewis and R. R. Holden, “DC Bead Embolic Drug-eluting Bead: Clinical Application in the Locoregional Treatment of Tumours,” Expert Opinion on Drug Delivery 8, no. 2 (2011): 153–169.

[405] C. Aliberti, G. Fiorentini, P. C. Muzzio, et al., “Trans-arterial Chemoembolization of Metastatic Colorectal Carcinoma to the Liver Adopting DC Bead, Drug-eluting Bead Loaded With Irinotecan: Results of a Phase II Clinical Study,” Anticancer Research 31, no. 12 (2011): 4581–4587.

[406] R. Bandyopadhyay, K. Selvakumar, J. M. M. Mohamed, and D. Ebrahim, “A Review of Process Validation of Hydrogel Formulation,” International Journal of Pharmaceutical and Phytopharmacological Research 14 (2024): 36–42.

[407] J. M. Alonso, J. Andrade del Olmo, R. Perez Gonzalez, and V. Saez-Martinez, “Injectable Hydrogels: From Laboratory to Industrialization,” Polymers 13, no. 4 (2021): 650.

[408] R. Szoleczky, M. Budai-Szűcs, E. Csányi, et al., “Analytical Quality by Design (AQbD) Approach to the Development of in Vitro Release Test for Topical Hydrogel,” Pharmaceutics 14, no. 4 (2022): 707.

[409] M. C. Catoira, J. González-Payo, L. Fusaro, M. Ramella, and F. Boccafoschi, “Natural Hydrogels R&D Process: Technical and Regulatory Aspects for Industrial Implementation,” Journal of Materials Science: Materials in Medicine 31, no. 8 (2020): 64.

[410] Z. Tang, L. Deng, J. Zhang, et al., “Intelligent Hydrogel-Assisted Hepatocellular Carcinoma Therapy,” Research 7 (2024): 0477.

[411] J. Shi, L. Yu, and J. Ding, “PEG-based Thermosensitive and Biodegradable Hydrogels,” Acta Biomaterialia 128 (2021): 42–59.

[412] Z. Li, P. Song, G. Li, et al., “AI Energized Hydrogel Design, Optimization and Application in Biomedicine,” Materials Today Bio 25 (2024): 101014.

RIGHTS & PERMISSIONS

2026 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.