Schematic illustration of the thermosensitive bi‐adjuvant hydrogel (FSP‐RZ‐BPH). a) Formation of FSP‐RZ‐BPH. The schematic diagram shows that R848, Zn2+ and FSPs are separately loaded on the BSA‐PEG to form a hydrogel skeleton, and its aqueous solution can form a hydrogel at 37 °C. b) Mechanism of synergistic proinflammatory effect of R848 + Zn2+ (RZ). R848 is a TLR7/8 agonist, which inhibits the degradation of STING by activating NF‐κB molecules, thereby promoting the Zn2+‐activated cGAS‐STING pathway. c) Schematic diagram to illustrate the immune response induced by FSP‐RZ‐BPH in vivo. Combined application of RZ can not only directly activate intratumoral reactive oxygen species (ROS), but also have pro‐inflammatory effects on DCs, T cells, NK cells and macrophages. Activation of DCs promotes the presentation of FSPs, generating a large number of effector T cells in the lymph nodes, which eventually leads to the increase of tumor‐infiltrating NRTs to kill tumor cells. In particular, sufficient tumor neoantigens released by ROS‐induced tumor cell death and the sustained immune activation of FSP‐RZ‐BPH endows T cells epitope spreading to maintain long‐term anti‐tumor immune responses.
