An injectable supramolecular hydrogel as a self-drug-delivery system for local chemoimmunotherapy against melanoma

Skin-cancer melanoma caused 57k death in 2020. Some of the available therapies are: topical application of a gel loaded with an anti-skin cancer drug and intravenous injection of immune cytokines; however, both the approaches have drawbacks such as inefficient internalization of the drug in cancer cells and a short half-life with severe side effects, respectively. Interestingly, we observed for the first time that a subcutaneously implanted hydrogel designed and synthesized by coordinating NSAIDs and 5-AP with Zn(II) can effectively combat melanoma cell (B16-F10)-induced tumors in C57BL/6 mice. Both in vitro and in vivo results show that it can effectively reduce PGE₂ expression, consequently upregulating IFN-γ and IL-12 that eventually engage M1-macrophages for activating T cells (CD8⁺), triggering apoptosis. This unique all-in-one self-drug-delivery approach, wherein the hydrogel implant is made from the drug molecules itself providing both chemotherapy and immunotherapy in combating deadly melanoma, highlights the supramolecular chemistry-based bottom-up approach in cancer therapy.