Therapeutic potential of a JHCF4-based fucoidan hydrogel for localized chemotherapy of hepatocellular carcinoma

• JHCF4-based hydrogel loaded with doxorubicin (J-H-DOX): a potent source of anticancer agent. • J-H-DOX was developed and prepared for orthotopic hepatoma treatment in a mice model. • J-H-DOX mediated by an increase in cell apoptosis and decrease in tumor angiogenesis was found. Local chemotherapy based on polymeric drug delivery systems has gained increasing attention for solid tumor treatment. In this study, a fucoidan fraction (JHCF4) extracted from Sargassum fusiforme was oxidized to produce aldehyde groups and subsequently crosslinked with ε-polylysine to fabricate an injectable hydrogel (J-H). Doxorubicin (DOX) was loaded into the hydrogel to form J-H-DOX. Physicochemical characterization showed that the hydrogel possessed good injectability, self-healing ability, biodegradability, and sustained drug release properties. In vitro studies demonstrated that JHCF4 significantly inhibited the proliferation of H22 hepatoma cells, indicating its inherent anticancer potential. Based on this, J-H, an injectable hydrogel, was constructed by crosslinking oxidized JHCF4 with ε-polylysine, and subsequently loaded with DOX to form J-H-DOX. In vivo evaluation using an orthotopic hepatocellular carcinoma (HCC) mouse model showed that J-H-DOX effectively suppressed tumor growth by inducing apoptosis, reducing cell proliferation, and inhibiting angiogenesis, outperforming both J-H and free DOX treatments. These findings suggest that JHCF4 possesses inherent anticancer activity and the hydrogel-based delivery system further enhances its therapeutic potential for localized chemotherapy in HCC. Schematic illustration of preparation of JHCF4-based hydrogel co-loaded with DOX (J-H-DOX), and synergy mechanism of J-H-DOX for the treatment of orthotopic hepatoma in a mice model.