An orally administered bacterial membrane protein nanodrug ameliorates doxorubicin cardiotoxicity through alleviating impaired intestinal barrier  

作　　者：Zhen Li Junyue Xing Xiaohan Ma Wanjun Zhang Chuan Wang Yingying Wang Xinkun Qi Yanhui Liu Dongdong Jian Xiaolei Cheng Yanjie Zhu Chao Shi Yongjun Guo Huan Zhao Wei Jiang Hao Tang 

机构地区：[1]National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine,Central China Subcenter of National Center for Cardiovascular Diseases,Henan Cardiovascular Disease Center,Fuwai Central-China Cardiovascular Hospital,Central China Fuwai Hospital of Zhengzhou University,Zhengzhou,450046,China [2]Henan Key Laboratory of Chronic Disease Management,Central China Fuwai Hospital of Zhengzhou University,Zhengzhou,Henan,451464,China [3]Zhengzhou Key Laboratory of Cardiovascular Aging,Central China Fuwai Hospital of Zhengzhou University,Zhengzhou,Henan,451464,China [4]Department of Hematology,Henan Provincial People’s Hospital,Zhengzhou,Henan,450003,China [5]Department of Oncology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,China [6]Department of Anesthesiology,Affiliated Drum Tower Hospital of Medical School of Nanjing University,Nanjing,Jiangsu,210008,China [7]Department of Pathology,Central Hospital of Kaifeng City,Kaifeng,Henan,475000,China [8]Henan Key Laboratory of Molecular Pathology,Department of Molecular Pathology,The Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou,Henan,450008,China

出　　处：《Bioactive Materials》2024年第7期517-532,共16页生物活性材料（英文）

基　　金：supported by National Natural Science Foundation of China (No.32100093,and 82100294);Natural Science Foundation of Henan Province (No.232300421175);Medical Science and Technology Project of Henan Province (SBGJ202302032);Henan Provincial Joint Fund of Science and Technology Research and Development Program (225200810075);The Young Elite Scientists Sponsorship Program by Henan Association for Science and Technology (Grant 2024HYTP048).

摘　　要：The cardiotoxicity caused by Dox chemotherapy represents a significant limitation to its clinical application and is a major cause of late death in patients undergoing chemotherapy.Currently,there are no effective treatments available.Our analysis of 295 clinical samples from 132 chemotherapy patients and 163 individuals undergoing physical examination revealed a strong positive correlation between intestinal barrier injury and the development of cardiotoxicity in chemotherapy patients.We developed a novel orally available and intestinal targeting protein nanodrug by assembling membrane protein Amuc_1100(obtained from intestinal bacteria Akkermansia muciniphila),fluorinated polyetherimide,and hyaluronic acid.The protein nanodrug demonstrated favorable stability against hydrolysis compared with free Amuc_1100.The in vivo results demonstrated that the protein nanodrug can alleviate Dox-induced cardiac toxicity by improving gut microbiota,increasing the proportion of short-chain fatty acid-producing bacteria from the Lachnospiraceae family,and further enhancing the levels of butyrate and pentanoic acids,ultimately regulating the homeostasis repair of lymphocytes in the spleen and heart.Therefore,we believe that the integrity of the intestinal barrier plays an important role in the development of chemotherapy-induced cardiotoxicity.Protective interventions targeting the intestinal barrier may hold promise as a general clinical treatment regimen for reducing Dox-induced cardiotoxicity.

关 键 词：Doxorubicin cardiotoxicity Intestinal barrier Protein delivery Oral nanodrugs Homeostasis of lymphocytes 

分 类 号：TB383[一般工业技术—材料科学与工程]