Engineered Microcystis aerugiosa Hydrogel as an Anti-Tumor Therapeutic by Augmenting Tumor Immunogenicity and Immune Responses

Cancer immunotherapy holds great promise but is generally limited by insufficient induction of anticancer immune responses. In this work, Microcystis aerugiosa (MA) is observed to act as an immune stimulator, which activates the cGAS-STING and IRF-signaling pathways of dendritic cells (DCs), induces immunostimulatory factors production, eventually resulting in the death of tumor cells by promoting cytotoxic CD8+ T cells infiltration. To further enhance the tumor immunogenicity, MA is engineered with polydopamine (PDA) and assembled in injectable Pluronic F127 hydrogels (denoted as MA@PDA-F127). The introduction of PDA endows the MA@PDA-F127 with photothermal therapy capability, which enhances the immunogenicity by in situ exposing damage-associated molecular patterns and tumor antigens from dying tumor cells. Importantly, the surface-rich reaction sites in thermosensitive MA@PDA-F127 hydrogels capture antigens, facilitating long retention of antigens exposure and enhancing DCs maturation for advanced anti-tumor immune response. Accordingly, in situ administration of MA@PDA-F127 hydrogels in a single dose achieves efficient eradication of both primary and distant tumors in an orthotopic tumor metastasis model. Furthermore, this hydrogel can sensitize immune checkpoint inhibitor therapy and enhance T cell infiltration in a murine tumor model. Collectively, MA@PDA-F127 hydrogel offers an effective anti-tumor therapeutic by augmenting tumor immunogenicity and activating a systematic immune response.