Abstract
Biopolymer-based hydrogels offer adaptable platforms for localized cancer therapy by regulating administration, tissue retention, payload protection, and therapeutic release. This review critically examines polysaccharide-, protein-, peptide-, and polynucleotide-based hydrogels, relating polymer composition, crosslinking, network architecture, swelling, degradation, and payload interactions to pharmaceutical and biological performance. Physical, chemical, enzymatic, and ionic gelation strategies are evaluated alongside diffusion-, swelling-, affinity-, and degradation-controlled release and their mathematical interpretation. Macrogels, microgels, nanogels, and hybrid systems are compared according to administration route, disposition, and oncology-relevant function. The review further distinguishes local placement, passive accumulation, ligand-mediated cellular interactions, and endogenous or externally triggered release. Applications in chemotherapy, radiotherapy, immunotherapy, hyperthermia, and phototherapy are assessed across colorectal, gastric, liver, pancreatic, and breast cancers. Marketed devices, patented technologies, clinically evaluated systems, and regulatory considerations are also examined. Despite extensive preclinical development, translation remains constrained by polymer variability, incomplete pharmaceutical characterization, sterilization and scale-up challenges, uncertain degradation and clearance, and limited clinically representative evidence. Progress will depend on clinically defined product design, reproducible manufacturing, quantitative disposition and safety assessment, and demonstration of meaningful benefit over existing therapeutic or procedural alternatives.