Endogenous Fe^(2+)- triggered self- targeting nanomicelles for self- amplifying intracellular oxidative stress  

作　　者：Zhongxiong Fan Guoyu Xia Qingluo Wang Shiduan Chen Jianmin Li Zhenqing Hou Ziwen Jiang Juan Feng 

机构地区：[1]School of Pharmaceutical Sciences and Institute of Materia Medica,Xinjiang University,Urumqi,China [2]College of Materials,Xiamen University,Xiamen,China [3]Department of Gynecology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing Maternal and Child Health Care Hospital,Beijing,China [4]Department of Hematology,The First Affiliated Hospital of Xiamen University and Institute of Hematology,School of Medicine,Xiamen University,Xiamen,China

出　　处：《Animal Models and Experimental Medicine》2025年第2期307-321,共15页动物模型与实验医学(英文)

基　　金：We acknowledge the financial support from the National Natural Science Foundation of China(82000152);Key Research and Development Program in Xinjiang Uygur Autonomous Region(2023B02030 and 2023B02030-1);Autonomous Region Universities Basic Research Funds Research Projects-Cultivation Projects(XJEDU2023P017);Natural Science Foundation of Xinjiang Uygur Autonomous Region(2022D01C698);the Xinjiang Uygur Autonomous Region Tianchi Talent Introduction Program-Young Doctor(51052300514).

摘　　要：Background:Artesunate(ASA)acts as an•O_(2)^(-)source through the breakdown of en-doperoxide bridges catalyzed by Fe2+,yet its efficacy in ASA-based nanodrugs is lim-ited by poor intracellular delivery.Methods:ASA–hyaluronic acid(HA)conjugates were formed from hydrophobic ASA and hydrophilic HA by an esterification reaction first,and then self-targeting nanomi-celles(NM)were developed using the fact that the amphiphilic conjugates of ASA and HA are capable of self-assembling in aqueous environments.Results:These ASA–HA NMs utilize CD44 receptor-mediated transcytosis to greatly enhance uptake by breast cancer cells.Subsequently,endogenous Fe^(2+)from the tumor catalyzes the released ASA to produce highly toxic•O₂-radicals to kill tumor cells,although sustained tumor growth inhibition can be achieved via in vivo experiments.Conclusions:Self-targeting NMs represent a promising strategy for enhancing ASA-based treatments,leveraging clinically approved drugs to expedite drug development and clinical research in oncology.

关 键 词：nanomicelles non-Fenton oxidative stress reactive oxygen species self-targeting 

分 类 号：R73[医药卫生—肿瘤]