Coordination-strengthened Rhein/Pectin@Zn dual-network hydrogel for local antitumor therapy

Local therapeutic platforms capable of concurrent tumor-cell elimination and antiangiogenic activity are urgently needed. This study presents a Rhein/Pectin@Zn hydrogel fabricated through supramolecular self-assembly and metal-coordination crosslinking and administered by dual-syringe in situ gelation. Hydrogels prepared under standardized ex vivo crosslinking conditions display a porous microstructure, stable gel characteristics, shear-dependent flow behavior, and accelerated cargo release under acidic conditions. Biological evaluations indicate antiproliferative and pro-apoptotic effects against tumor cells, together with reduced endothelial angiogenic signaling. Repeated intratumoral delivery in a subcutaneous B16 melanoma model reduced endpoint tumor volume and weight without overt major-organ histopathological abnormalities in the displayed fields. Integrated transcriptomic and molecular analyses implicated cell-cycle checkpoint disruption and apoptosis-associated signaling in the observed antitumor response. Collectively, this work positions Rhein/Pectin@Zn as an in situ-forming hydrogel for local cancer therapy.