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

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.