A self-assembled nanomicelle-based "one stone for two birds" strategy for precision therapy of hepatic ischemia-reperfusion injury  

作　　者：Mengyuan Yu Jiongjie Yu Yujie Zhou Zhi Liang Hong Tang Changbiao Li Qingyang Que Hangxiang Wang Haiyang Xie Xiao Xu 

机构地区：[1]The Fourth School of Clinical Medicine,Zhejiang Chinese Medical University,Hangzhou 310053,China [2]Zhejiang University School of Medicine,Hangzhou 310058,China [3]Division of Hepatobiliary and Pancreatic Surgery,Department of Surgery,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China [4]NHC Key Laboratory of Combined Multi-organ Transplantation,Hangzhou 310003,China [5]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,Hangzhou 310003,China [6]School of Clinical Medicine,Hangzhou Medical College,Hangzhou 310014,China [7]Institute of Translational Medicine,Zhejiang University School of Medicine,Hangzhou 310000,China

出　　处：《Nano Research》2025年第2期627-640,共14页纳米研究(英文版)

基　　金：This research gained support from the National Key Research and Development Program of China(No.2021YFA1100500);the Major Research Plan of the National Natural Science Foundation of China(No.92159202);the National Natural Science Foundation of China(Nos.32171368 and 81930016);State Key Laboratory for Diagnosis and Treatment of Infectious Diseases(No.zz202310);the Non profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2023-PT320-02);the International Science and Technology Cooperation Project of Zhejiang province.

摘　　要：Hepatic ischemia-reperfusion injury(IRI)is an intricate and inevitable physiological event occurred in the liver transplantation(LT)and it is of paramount importance to devise novel and efficient methods to ameliorate IRl.Herein,we report a"one stone for two birds"strategy for IRI therapy.In this study,we engineered carvacrol-artesunate(CAR-ART)nanoparticles(CANPs)utilizing CAR and ART as precursor monomers and simulated IRl in an in vivo mouse model.Our research results indicate that CANPs proficiently surmount the constraints linked with the solitary components utilized in preceding studies such as water solubility,stability,and biocompatibility.Furthermore,they exhibit a distinctive accumulation in the liver.From an immunological standpoint,CANPs have been observed to significantly impede the accumulation and activation of various immune cells such as macrophages,neutrophils,and Kupffer cells.This results in the restoration of the hepatic immune cell distribution to a state akin to that of a normal liver.Furthermore,CANPs markedly inhibit the accumulation of a multitude of pro-inflammatory cytokines.Cellularly,it has been observed that CANPs significantly hinder the onset of ferroptosis in hepatocytes.This is accomplished by inhibiting the accumulation of crucial enzymes such as long-chain-fatty-acid-CoA ligase 4(ACSL4),as well as associated lipid oxidation intermediates like malondialdehyde(MDA),which are relevant to the process of ferroptosis.Consequently,a solitary intravenous administration of CANPs has the potential to simultaneously inhibit ferroptosis of hepatocytes and normalize proinflammatory immune cells,one stone for two birds.In conclusion,CANPs may serve as a promising multi-bioactive nanotherapeutic agent and a bioresponsive targeting delivery nanocarrier,offering a potentially effective treatment strategy for hepatic IRI.

关 键 词：carvacrol(CAR) artesunate(ART) nanoparticles ischemia-reperfusion injury(IRI) ferroptosis 

分 类 号：R57[医药卫生—消化系统]