Schottky Heterojunction Realizes In Situ Vaccine‐Like Antitumor Efficacy and Microenvironment Remodeling Upon Near‐Infrared Laser Response in Cold Tumors

Abstract

AbstractCold tumor is one of the most refractory tumors due to its low immunogenicity and absence of T cell infiltration. The immunotherapeutic effect of near‐infrared (NIR) responsive nanomaterials on tumors is far from satisfactory. Herein, ultrasmall γ‐MnO2 nanodots are anchored on the intrinsic metallic Ti3C2(OH)2, modified with bovine serum albumin, to realize a Schottky heterojunction (labeled as TC‐MnO2@BSA), which can be utilized to reshape the cold tumor microenvironment (TME) through in situ vaccine‐like antitumor effect. The Schottky heterojunction endows TC‐MnO2@BSA with improved photothermal conversion and reactive oxygen species (ROS) generation. Excess ROS and heat lead to tumor immunogenic death (ICD) and abundant damaged double‐strain DNA releasing into TME, coordinated with TC‐MnO2@BSA‐derived Mn2+, magnifying the cGAS‐STING signaling pathway, eventually promoting antigen presentation of dendritic cells and infiltration of T cells. Such a NIR‐activated nanovaccine can achieve complete ablation of tumors while robust activating systemic antitumor immune response. Furthermore, it inhibits the growth of abscopal tumors through dramatically “heating” their cold TME. This work introduces a universal strategy to magnify the photothermal and immune adjuvant effect through the gain of Schottky heterostructure, as a novel paradigm to construct the multifunctional in situ nanovaccine.