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 tre...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.展开更多
基金supported by National Natural Science Foundation of China (No.32100093,and 82100294)Natural Science Foundation of Henan Province (No.232300421175)+2 种基金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).
文摘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.
