Destroying pathogen-tumor symbionts synergizing with catalytic therapy of colorectal cancer by biomimetic protein-supported single-atom nanozyme  

作　　者：Xinyue Wang Qian Chen Yefei Zhu Kairuo Wang Yongliang Chang Xiawei Wu Weichao Bao Tongcheng Cao Hangrong Chen Yang Zhang Huanlong Qin 

机构地区：[1]Nanomedicine and Intestinal Microecology Research Center,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai 200072,PR China [2]State Key Laboratory of High Performance Ceramics and Superfine Microstructure,Shanghai Institute of Ceramics,Shanghai 200050,China [3]Shanghai Key Lab of Chemical Assessment and Sustainability,School of Chemical Science and Engineering,Tongji University,1239 Siping Road,Shanghai 200092,China [4]Precision Medicine Center,Taizhou Central Hospital,999 Donghai Road,Taizhou 318000 Zhejiang,China

出　　处：《Signal Transduction and Targeted Therapy》2023年第8期3837-3848,共12页信号转导与靶向治疗(英文)

基　　金：This article was supported by the National Natural Science Foundation of China(Grant Nos.81730102,32271384);Shanghai Basic Research Program(Grant No.20JC1411702);Shanghai Science and Technology Program(Grant No.20ZR1456100);Basic Study on Public Projects in Zhejiang Province(Grant No.LGF20H060017);the National Key Research and Development Program of China(Grant No.2021YFB3801001);China Postdoctoral Science Foundation(Grant No.2021M702484);Shanghai Post-doctoral Excellence Program(Grant No.2020382);Shanghai General Hospital Integrated Traditional Chinese and Western Medicine Special Project(Grant No.ZHYY-ZXYJHZX-202105).The authors would like to thank the workers from Shiyanjia Lab(www.shiyanjia.com)for tests of XANES and EXAFS.

摘　　要：The crucial role of intratumoral bacteria in the progression of cancer has been gradually recognized with the development of sequencing technology.Several intratumoral bacteria which have been identified as pathogens of cancer that induce progression,metastasis,and poor outcome of cancer,while tumor vascular networks and immunosuppressive microenvironment provide shelters for pathogens localization.Thus,the mutually-beneficial interplay between pathogens and tumors,named“pathogentumor symbionts”,is probably a potential therapeutic site for tumor treatment.Herein,we proposed a destroying pathogen-tumor symbionts strategy that kills intratumoral pathogens,F.nucleatum,to break the symbiont and synergize to kill colorectal cancer(CRC)cells.This strategy was achieved by a groundbreaking protein-supported copper single-atom nanozyme(BSA-Cu SAN)which was inspired by the structures of native enzymes that are based on protein,with metal elements as the active center.BSA-Cu SAN can exert catalytic therapy by generating reactive oxygen species(ROS)and depleting GSH.The in vitro and in vivo experiments demonstrate that BSA-Cu SAN passively targets tumor sites and efficiently scavenges F.nucleatum in situ to destroy pathogentumor symbionts.As a result,ROS resistance of CRC through elevated autophagy mediated by F.nucleatum was relieved,contributing to apoptosis of cancer cells induced by intracellular redox imbalance generated by BSA-Cu SAN.Particularly,BSA-Cu SAN experiences renal clearance,avoiding long-term systemic toxicity.This work provides a feasible paradigm for destroying pathogen-tumor symbionts to block intratumoral pathogens interplay with CRC for antitumor therapy and an optimized trail for the SAN catalytic therapy by the clearable protein-supported SAN.

关 键 词：COLORECTAL ELEVATED CATALYTIC 

分 类 号：R735.34[医药卫生—肿瘤]