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 deaths estimated for 2026 in the 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.