Citation: 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. Reversing artemisinin resistance by leveraging thermo-responsive nanoplatform to downregulating GSH[J]. Chinese Chemical Letters, ;2024, 35(6): 108929. doi: 10.1016/j.cclet.2023.108929 shu

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

Yong-Dan Zhao ^{a, b} ,
Yidan Wang ^a ,
Rongrong Wang ^a ,
Lina Chen ^c ,
Hengtong Zuo ^a ,
Xi Wang ^a ,
Jihong Qiang ^a ,
Geng Wang ^a ,
Qingxia Li ^a ,
Canqi Ping ^a ,
Shuqiu Zhang ^{a, *,} ,
Hao Wang ^{b, *,}

a.
School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China
b.
National Center for Nanoscience and Technology, Beijing 100190, China
c.
Artemisinin Research Center, Institute of Chinese Materia Medica, Beijing 100700, China

shuqiu.zhang@sxmu.edu.cn

wanghao@nanoctr.cn

Received Date: 28 June 2023
Revised Date: 9 August 2023
Accepted Date: 10 August 2023
Available Online: 13 August 2023

Figures(5)

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.
- Nanomedicines,
- Drug delivery,
- Artemisinins resistance,
- Malaria,
- Glutathione
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