Hydrogel-dependent strategies to modulate the tumor microenvironment for improved anti-tumor treatment.

Hydrogel-based platforms for localized cancer treatment: Design strategies for precision therapeutic delivery.

Cancer remains a leading cause of global mortality, with over 1.2 million cancer related death estimated for 2026 in EU alone. Although advances in chemotherapy and immunotherapy have improved cancer treatment, systemic administration of these agents often results in severe off-target toxicity and limited efficacy, due to rapid clearance and poor tumor penetration. This review examines the pivotal role of hydrogels in transforming drug delivery strategies for cancer therapy. Through sustained, site-specific release, hydrogel platforms overcome key limitations of systemic therapy by providing controlled, localized delivery of a wide range of anticancer agents within the tumor microenvironment (TME). The review explores the chemical and physical modifications that enable these hydrogel-based dynamic interfaces to respond to physiological triggers, particularly the acidic TME, as well as other relevant cues. The analysis is supported by selective case studies across diverse cancer types, including osteosarcoma, hepatocellular carcinoma, breast, lung, prostate and pancreatic cancers. By synchronizing drug(s) release with biological cues (such as TME pH, enzymes, or redox conditions) and improving the stability of fragile cargo (e.g., immunomodulatory agents, nucleic acid-based drugs), these platforms offer a robust strategy for enhancing the safety and efficacy of localized cancer treatment. Key formulation principles are evaluated as context-dependent trade-offs, including injectability, gelation kinetics, mesh size, precursor chemistry, stimuli-responsiveness, biodegradation, mechanical stability and host response. Together, these features constitute the core design framework guiding current developments in hydrogel-based immunotherapeutic systems. Overall, successful translation of hydrogel-based cancer therapy will require moving beyond proof-of-concept drug loading toward indication-specific platforms that demonstrate clinically meaningful advantages over existing standards of care.

Next-generation nanocarriers for synergistic Chemoimmunotherapy: engineering the tumor microenvironment for precision cancer treatment

Chemoimmunotherapy has emerged as a promising strategy for cancer treatment by combining the cytotoxic effects of chemotherapy with the durable immune activation achieved through immunotherapy. However, clinical translation remains limited by poor tumor targeting, systemic toxicity, heterogeneous tumor microenvironments, and inadequate immune activation. Nanocarrier-based delivery systems have recently gained considerable attention because they enable co-delivery of chemotherapeutic and immunotherapeutic agents, controlled drug release, enhanced tumor accumulation, and modulation of the tumor microenvironment. This review summarizes the recent advances in lipid-, polymer-, inorganic-, and biomimetic nanocarriers for synergistic Chemoimmunotherapy. The review also discusses emerging delivery platforms including metal-organic frameworks, extracellular vesicles, stimuli-responsive systems, tumor accumulation mechanisms, current clinical progress, and future translational challenges.

Nanogel for Cancer Drug Delivery: A Review of Recent Advances and Therapeutic

Cancer is one of the leading causes of death around the globe. The conventional cancer therapies have several drawbacks, like non-specific biodistribution, poor stability, and significant systemic toxicity. Nanogels are increasingly recognized as a promising type of nanocarrier for cancer therapy because of their structural versatility, biocompatibility, and remarkable drug-loading efficiency. As cross-linked polymeric hydrogel nanoparticles, they offer multiple benefits, including enhancing the solubility of hydrophobic drugs, enabling controlled and stimulus-responsive release, improving tumour-specific delivery through the enhanced permeability and retention (EPR) effect, and reducing systemic toxicity. Recent progress in nanogel engineering has introduced smart modifications such as pH-, temperature-, enzyme-, and redox-responsive designs, which allow exact and localized drug release within the tumor microenvironment. The present review provides a comprehensive overview of nanogels, their types, and effects on various types of cancers.

Design of Multi-Stimuli Responsive Nanocarriers for Co-delivery of Phytochemicals and Immune Modulators: A Synergistic Approach to Overcoming Tumor Resistance

Polymeric Nanoparticles for Precision Tumor Immunotherapy: Rational Design Strategies and Spatiotemporal Immune Activation

Abstract Malignant tumors remain one of the most serious challenges to global health. Although chemotherapy and targeted therapy are available treatment options, their effectiveness is often limited by the complexity of the tumor microenvironment (TME). In recent years, immunotherapy has demonstrated significant potential in harnessing the immune system to combat cancer. Polymeric nanoparticles (PNPs) have emerged as versatile platforms for cancer immunotherapy, offering favorable biocompatibility, tunable size, and surface functionalization for targeted delivery. In this review, we critically evaluate PNP design strategies, emphasizing stimuli-responsive release mechanisms that enable spatiotemporally controlled drug delivery within the TME, thereby enhancing efficacy and minimizing systemic toxicity. We further highlight PNP-enabled synergistic therapies, including photodynamic, chemodynamic, and sonodynamic therapies, that induce immunogenic cell death (ICD) and potentiate antitumor immunity, as well as PNP-based vaccines (RNA, peptide, and in situ) that activate dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs). Nevertheless, the clinical translation of PNP-based therapies is constrained by multiple factors, including manufacturing scalability, emulsifier-related toxicity, rapid RES clearance, inherent immunogenicity, and the heterogeneity of the TME. By bridging material engineering with immunological barriers and translational challenges, this review provides a critical framework for designing next-generation PNP immunotherapies toward personalized cancer treatment.

Harnessing chitosan-based biomaterials for advanced cancer immunotherapy: from nanocarriers to tumor microenvironment modulation

Cancer immunotherapy has transformed oncology, however, its clinical efficacy remains limited by immunosuppressive tumor microenvironments (TMEs), poor therapeutic delivery, systematic toxicity, treatment resistance. Chitosan, a biocompatible and biodegradable polysaccharide, has emerged as a versatile biomaterial capable of addressing these challenges through both intrinsics immunomodulatory activity and advanced drug-delivery functions. This review summarizs recent advances in chitosan-based biomaterials for cancer immunotherapy, highlighting their ability to activate innate and adaptive immune responses through pathways involving patterns recognition receptors, cyclic GMP-AMP synthase (cGAS)=simulator of interferon genes (STING) signaling, dendric cells (DCs)macrophages, natural killer (NK) cells and T lymphocytes. The design and application of chitosan-based nanoparticles and hydrogels as platformsfor delivering cytokines, nucleic acids, immune adjuvant, cancer vaccines and immune checkpoint therapeutics are discussed. Particular attention is given to their roles in TME remodeling, sustained local drug release, postsurgical immunotherapy, and combination approaches that integrate chemotherapy, radiotherapy (RT), phototherapy and immunotherapy. Emerging strategies, including stimuli-responsive systems, biomimetic formulations, and multifunctional nanoplatforms are also discussed. Finally, we discuss the current translational current translational challenges and future perspectives, emphasizing the potential of chitosan-based biomaterials to enhance antitumor immunity and improve clinical outcomes in cancer immunotherapy. Chitosan biomaterials enhance antitumor immunity through intrinsic immunomodulatory activity. Chitosan nanoparticles and hydrogels enable efficient delivery of immunotherapeutic agents. Chitosan-based systems remodel the tumor microenvironment and promote immune activation. Combination therapies that integrate chitosan platforms improve therapeutic efficacy and reduce toxicity. Stimuli-responsive and multifunctional chitosan nanoplatforms offer promising strategies for precision cancer immunotherapy.