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

Abstract Tumor vaccine uses 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, and hypoxic tumor microenvironment, which leads poor therapeutic effect. To overcome the defects of traditional tumor vaccine, a photosensitive gel vaccine (KMO/DOX&NA) with enzyme-like properties was constructed by using the reduction reaction of oleic acid in potassium permanganate environment to accurate delivery of GSH-triggered chemotherapy drugs doxorubicin (DOX) and nattokinase (NA). Moreover, KMO/DOX&NA contained MnO 2 has peroxidases-like properties, which can react with H 2 O 2 in TME to generate oxygen. Besides, MnO 2 has excellent photothermal conversion performance once excited by near-infrared irradiation, which can induce the immunogenic death of tumor cells and improve the permeability of cell membrane, when the temperature exceeds 45 o C. Importantly, Mn 2+ contained in KMO/DOX&NA 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 KMO/DOX&NA can degrade extracellular matrix components, thus reducing tumor hardness and enhancing intra-tumor perfusion. In general, this study proposed KMO/DOX&NA in-situ vaccine with enzyme-like properties, which can reshape the tumor immunosuppression microenvironment to achieve “one injection, multiple therapies” as well as provide a new idea for the later development of more smarter and more efficient tumor vaccines.