Nanomotor-based H<sub>2</sub>S donor with mitochondrial targeting function for treatment of Parkinson's disease.

Zhao, Zinan; Chen, Lin; Yang, Chunhao; Guo, Wenyan; Huang, Yali; Wang, Wenjing; Wan, Mimi; Mao, Chun et al. · Bioact Mater · 2024

basic_science · Level V

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Abstract

Reduction of endogenous hydrogen sulfide (H<sub>2</sub>S) is considered to have an important impact on the progress of Parkinson's disease (PD), thus exogenous H<sub>2</sub>S supplementation is expected to become one of the key means to treat PD. However, at present, it is difficult for H<sub>2</sub>S donors to effectively penetrate the blood brain barrier (BBB), selectively release H<sub>2</sub>S in brain, and effectively target the mitochondria of neuron cells. Herein, we report a kind of nanomotor-based H<sub>2</sub>S donor, which is obtained by free radical polymerization reaction between l-cysteine derivative modified-polyethylene glycol (PEG-Cys) and 2-methacryloyloxyethyl phosphorylcholine (MPC). This kind of H<sub>2</sub>S donor can not only effectively break through BBB, but also be specifically catalyzed by cystathionine β-synthase (CBS) in neurons of PD site in brain and 3-mercaptopyruvate sulfurtransferase (3-MST) in mitochondria to produce H<sub>2</sub>S, endowing it with chemotaxis/motion ability. Moreover, the unique chemotaxis effect of nanomotor can realize the purpose of precisely targeting brain and the mitochondria of damaged neuron cytopathic diseases. This kind of nanomotor-based H<sub>2</sub>S donor is expected to enrich the current types of H<sub>2</sub>S donors and provide new ideas for the treatment of PD.