A Wurster-Type Covalent Organic Framework with Internal Electron Transfer-Enhanced Catalytic Capacity for Tumor Therapy

作者：Yang Liu, Huan Zhao, Shihuai Wang, Rui Niu, Shuai Bi, Wang‐Kang Han, Yinghui Wang, Shuyan Song, Hongjie Zhang, Yanli Zhao · 发表于：Journal of the American Chemical Society · 年份：2024 · DOI：10.1021/jacs.4c05555 · 被引用次数：65 · 研究领域：Covalent Organic Framework Applications、Metal-Organic Frameworks: Synthesis and Applications、Advanced Photocatalysis Techniques

The low immunogenicity of tumors, along with the abnormal structural and biochemical barriers of tumor-associated vasculature, impedes the infiltration and function of effector T cells at the tumor site, severely inhibiting the efficacy of antitumor immunotherapy. In this study, a cobaloxime catalyst and STING agonist (MSA-2)-coloaded Wurster-type covalent organic framework (Co-TB COF-M) with internal electron transfer-enhanced catalytic capacity was developed as a COF-based immune activator. The covalently anchored cobaloxime adjusts the energy band structure of TB COF and provides it with good substrate adsorption sites, enabling it to act as an electron transmission bridge between the COF and substrate in proton reduction catalytic reactions. This property significantly enhances the sonodynamic catalytic performance. Under sono-irradiation, Co-TB COF-M can produce a substantial amount of reactive oxygen species (ROS) to induce Gasdermin D-mediated pro-inflammatory pyroptosis, thereby effectively enhancing the immunogenicity of tumors. Furthermore, MSA-2 is specifically released in response to ROS at the tumor site, minimizing the off-target side effects. More importantly, Co-TB COF-induced STING activation normalizes tumor vasculature and increases the expression of endothelial T cell adhesion molecules, which greatly enhance the infiltration and function of effector T cells. Thus, Co-TB COF-M as an immune activator could remold the tumor microenvironment, leading to incre...