A biomimetic spore nanoplatform for boosting chemodynamic therapy and bacteria-mediated antitumor immunity for synergistic cancer treatment  

作　　者：Cuixia Zheng Lingling Sun Hongjuan Zhao Mengya Niu Dandan Zhang Xinxin Liu Qingling Song Weijie Zhong Baojin Wang Yun Zhang Lei Wang 

机构地区：[1]School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001,China [2]Huaihe Hospital of Henan University,Translational medicine Center,Kaifeng 475000,China [3]Pingyuan Lab,Henan Normal University,Xinxiang 453007,China [4]Gynecology,the Third Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China [5]Weihai Municipal Hospital,Cheeloo College of Medicine,Shandong University,Weihai 264200,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2024年第3期102-114,共13页亚洲药物制剂科学（英文）

基　　金：supported by the National Natural Science Foundation of China(No.82272847,82202318,82304417,82303529);The Henan Province Fund for Cultivating Advantageous Disciplines(No.222301420012);Central Plains science and technology innovation leading talent project(No.234200510005);The project tackling of key scientific and technical problems of Henan Provine(No.232102311163);China Postdoctoral Science Foundation(2022TQ0310,2023TQ0307,2023M730971)。

摘　　要：Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer.However,the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations.Furthermore,monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors.In this study,based on our discovery that spore shell(SS)of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity,we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy,chemodynamic therapy and antitumor immunity for synergistic cancer treatment.In detail,SS is separated from probiotic spores and then attached to the surface of liposome(Lipo)that was loaded with hemoglobin(Hb),glucose oxidase(GOx)and JQ1to construct SS@Lipo/Hb/GOx/JQ1.In tumor tissue,highly toxic hydroxyl radicals(·OH)are generated via sequential catalytic reactions:GOx catalyzing glucose into H_(2)O_(2)and Fe^(2+)in Hb decomposing H_(2)O_(2)into·OH.The combination of·OH and SS adjuvant can improve tumor immunogenicity and activate immune system.Meanwhile,JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response.In this manner,SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis.To summarize,the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.

关 键 词：Biomimetic spore shell Bacteria-mediated antitumor THERAPY Chemodynamic therapy Immunotherapy Tumor microenvironment 

分 类 号：R943[医药卫生—药剂学]