Gas-propelled nanomotors alleviate colitis through the regulation of intestinal immunoenvironment-hematopexis-microbiota circuits  

作　　者：Bo Xiao Yuqi Liang Ga Liu Lingshuang Wang Zhan Zhang Libin Qiu Haiting Xu Sean Carr Xiaoxiao Shi Rui LReis Subhas CKundu Zhenghua Zhu 

机构地区：[1]Department of Gastroenterology,the First Affiliated Hospital of Nanchang University,Nanchang 330006,China [2]College of Sericulture,Textile,and Biomass Sciences,Southwest University,Chongqing 400715,China [3]Department of Neurology,School of Medicine,Emory University,Atlanta,GA 30322,USA [4]Atlanta Veterans Affairs Medical Center,Decatur,GA 30033,USA [5]Department of Surgery,School of Medicine,Emory University,Atlanta,GA 30322,USA [6]Bs Research Group,I3Bs—Research Institute on Biomaterials,Biodegradables and Biomimetics,University of Minho,Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine,AvePark,Barco,Guimaraes 4805-017,Portugal

出　　处：《Acta Pharmaceutica Sinica B》2024年第6期2732-2747,共16页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(82072060,82360110,and 22008201);the Fundamental Research Funds for the Central Universities(SWU-XDPY22006,China);the Venture&Innovation Support Program for Chongqing Overseas Returnees(2205012980212766,China);the Distinguished Young Scholars of Chongqing(2022NSCQ-JQX5279,China);the Science and Technology Department of Jiangxi Province(20212BDH81019 and 20224BAB206073,China).

摘　　要：The progression of ulcerative colitis(UC)is associated with immunologic derangement,intestinal hemorrhage,and microbiota imbalance.While traditional medications mainly focus on mitigating inflammation,it remains challenging to address multiple symptoms.Here,a versatile gas-propelled nanomotor was constructed by mild fusion of post-ultrasonic CaO_(2) nanospheres with Cu_(2)O nanoblocks.The resulting CaO_(2)–Cu_(2)O possessed a desirable diameter(291.3 nm)and a uniform size distribution.It could be efficiently internalized by colonic epithelial cells and macrophages,scavenge intracellular reactive oxygen/nitrogen species,and alleviate immune reactions by pro-polarizing macrophages to the anti-inflammatory M2 phenotype.This nanomotor was found to penetrate through the mucus barrier and accumulate in the colitis mucosa due to the driving force of the generated oxygen bubbles.Rectal administration of CaO_(2)–Cu_(2)O could stanch the bleeding,repair the disrupted colonic epithelial layer,and reduce the inflammatory responses through its interaction with the genes relevant to blood coagulation,anti-oxidation,wound healing,and anti-inflammation.Impressively,it restored intestinal microbiota balance by elevating the proportions of beneficial bacteria(e.g.,Odoribacter and Bifidobacterium)and decreasing the abundances of harmful bacteria(e.g.,Prevotellaceae and Helicobacter).Our gas-driven CaO_(2)–Cu_(2)O offers a promising therapeutic platform for robust treatment of UC via the rectal route.

关 键 词：NANOMOTOR ANTI-INFLAMMATION Blood coagulation Immune regulation Hematopexis Microbiota rebalance Ulcerative colitis Rectal administration 

分 类 号：R730.53[医药卫生—肿瘤]