Photosensitive gel vaccine with enzyme-like properties for remodeling tumor microenvironment with STING activation for tumor synergistic therapy

Tumor vaccine utilizes tumor cells or tumor antigens to activate body’s immune system to clear tumors. However, the curative effect of tumor vaccine is easily influenced by tumor heterogeneity, as well as by hypoxic tumor microenvironment (TME) can promote tumor recurrence and metastasis. In this study, a photosensitive gel vaccine (OA&PG/DOX&NA) with enzyme-like properties was constructed via the reduction reaction of oleic acid (OA) in potassium permanganate (PG) environment to accurate delivery of chemotherapy drugs doxorubicin (DOX) and nattokinase (NA). OA&PG/DOX&NA contained MnO2 offers dual therapeutic advantages. Not only does it act as a catalase mimic to react with H2O2 in tumor tissues to generate oxygen, but it also function as a photothermal agent under NIR irradiation. The generated heat (> 45 ℃) simultaneously induces immunogenic cell death and increases cell membrane permeability. Importantly, OA&PG/DOX&NA contained Mn2+ can directly activate the interferon gene stimulating factor pathway, promote the maturation and antigen cross-presentation ability of dendritic cells, and then activate cytotoxic T lymphocytes and memory T lymphocytes to kill tumor cells. To promote the infiltration of DOX and immune cells in tumor tissues, NA released from OA&PG/DOX&NA can degrade extracellular matrix components, thus reducing tumor hardness and enhancing intra-tumor perfusion. In general, OA&PG/DOX&NA in-situ vaccine with enzyme-like properties, can reshape the immunosuppression TME to achieve “one injection, multiple therapies” in tumor therapy.