DOI: 10.1002/ame2.12468
Endogenous Fe2+-triggered self-targeting nanomicelles for self-amplifying intracellular oxidative stress
Zhongxiong Fan
Guoyu Xia
Qingluo Wang
Shiduan Chen
Jianmin Li
Zhenqing Hou
Ziwen Jiang
Juan Feng
Abstract：Background: Artesunate (ASA) acts as an ·O₂-source through the breakdown of endoperoxide bridges catalyzed by Fe 2+, yet its efficacy in ASA-based nanodrugs is limited 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 nanomicelles (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.
Keywords：nanomicellesnon-Fentonoxidative stressreactive oxygen speciesself-targeting
Publication Date：2025-02-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：15( 307-321 )