Naturally-derived injectable hydrogels for antitumor therapeutics

As novel localized drug delivery platforms, injectable hydrogels demonstrate significant potential in precision tumor therapy. By enabling spatiotemporally controlled drug release at target sites, they not only reduce systemic toxicity but also facilitate synergistic codelivery of chemotherapeutic agents, immunomodulators and gene therapy carriers. However, synthetic polymer-based hydrogel scaffolds face major challenges in clinical translation due to complex fabrication processes, potential immunogenicity and metabolic toxicity. In recent years, natural biomaterials such as chitosan, gelatin, and hyaluronic acid have emerged as preferred matrices for constructing antitumor hydrogel carriers, owing to their inherent biocompatibility, tunable biodegradability and clinical feasibility. This review systematically summarizes the structural advantages of natural biomaterials and their design principles in developing injectable hydrogels for antitumor applications, with particular focus on their cargo-loading mechanisms for diverse therapeutic agents. Additionally, it provides an in-depth discussion of key challenges in the clinical translation of natural material-based injectable hydrogels, aiming to guide the development of novel antitumor hydrogel platforms.