Constructing “smart” chelators by using an activatable prochelator strategy for the treatment of Wilson's disease

Chengcheng Wang; Roumin Wang; Lingzhou Zhao; Shasha Wang; Yan Liu; Jinhua Zhao; Yi Dong; Lingyan Liu; Peng Wei; Zhi-Ying Wu; Tao Yi

Redox Biology (Apr 2024)

Constructing “smart” chelators by using an activatable prochelator strategy for the treatment of Wilson's disease

Chengcheng Wang,
Roumin Wang,
Lingzhou Zhao,
Shasha Wang,
Yan Liu,
Jinhua Zhao,
Yi Dong,
Lingyan Liu,
Peng Wei,
Zhi-Ying Wu,
Tao Yi

Affiliations

Chengcheng Wang: State Key Laboratory for Modiﬁcation of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry and Chemical Engineering, Donghua University, Shanghai, 201620, China
Roumin Wang: Department of Neurology and Department of Medical Genetics in Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, 310000, China
Lingzhou Zhao: Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
Shasha Wang: State Key Laboratory for Modiﬁcation of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry and Chemical Engineering, Donghua University, Shanghai, 201620, China
Yan Liu: State Key Laboratory for Modiﬁcation of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry and Chemical Engineering, Donghua University, Shanghai, 201620, China
Jinhua Zhao: Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
Yi Dong: Department of Neurology and Department of Medical Genetics in Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, 310000, China
Lingyan Liu: State Key Laboratory for Modiﬁcation of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry and Chemical Engineering, Donghua University, Shanghai, 201620, China
Peng Wei: State Key Laboratory for Modiﬁcation of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry and Chemical Engineering, Donghua University, Shanghai, 201620, China; Corresponding author.
Zhi-Ying Wu: Department of Neurology and Department of Medical Genetics in Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, 310000, China; Corresponding author.
Tao Yi: State Key Laboratory for Modiﬁcation of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry and Chemical Engineering, Donghua University, Shanghai, 201620, China; Corresponding author.

Journal volume & issue: Vol. 70
p. 103076

Abstract

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Wilson's disease (WD) is a genetic disorder that primarily leads to the pathological accumulation of copper (Cu) in the liver, causing an abnormal increase in reactive oxygen species (ROS). The prevailing clinical therapy for WD involves lifelong use of Cu chelation drugs to facilitate Cu excretion in patients. However, most available drugs exert severely side-effects due to their non-specific excretion of Cu, unsuitable for long-term use. In this study, we construct a prochelator that enables precise and controlled delivery of Cu chelator drugs to the liver in WD model, circumventing toxic side effects on other organs and normal tissues. This innovative prochelator rapidly releases the chelator and the fluorescent molecule methylene blue (MB) upon activation by ROS highly expressed in the liver of WD. The released chelator coordinates with Cu, efficiently aiding in Cu removal from the body and effectively inhibiting the pathological progression of WD.

Published in Redox Biology

ISSN: 2213-2317 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.journals.elsevier.com/redox-biology/

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