Reversing artemisinin resistance by leveraging thermo-responsive nanoplatform to downregulating GSH  

作　　者：Yong-Dan Zhao Yidan Wang Rongrong Wang Lina Chen Hengtong Zuo Xi Wang Jihong Qiang Geng Wang Qingxia Li Canqi Ping Shuqiu Zhang Hao Wang 

机构地区：[1]School of Pharmacy,Shanxi Medical University,Taiyuan 030001,China [2]National Center for Nanoscience and Technology,Beijing 100190,China [3]Artemisinin Research Center,Institute of Chinese Materia Medica,Beijing 100700,China

出　　处：《Chinese Chemical Letters》2024年第6期392-397,共6页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.81803470 and 82173767)。

摘　　要：Artemisinin(ART)resistance has been an emerging clinical problem,severely compromising antimalarial efficacy and threatening the global malaria elimination campaign.Albeit intensive studies about the molecular mechanism for ART resistance are under way,no effective therapeutic targets for reversing resistance have been applied.Here,we explore glutathione(GSH)as a therapeutic target to develop a thermo-responsive nanoplatform to specifically co-deliver ART and GSH synthesis inhibitor(L-buthionine sulfoximine,BSO)in a sustained manner,effectively reversing ART resistance in vivo.By combining with BSO,ART exerts increased antimalarial activity with reduced half-maximal inhibitory concentration(IC50)by 7.43-fold in ART-resistant strains.This work reveals that the GSH in ART-resistant parasites can be a promising therapeutic target for reversing ART resistance,paving the way for developing drug candidates and intelligent nanomedicines in malaria therapy.

关 键 词：NANOMEDICINES Drug delivery Artemisinins resistance Malaria GLUTATHIONE 

分 类 号：TQ465[化学工程—制药化工]