Nanomotor-based H2S donor with mitochondrial targeting function for treatment of Parkinson's disease

Zinan Zhao; Lin Chen; Chunhao Yang; Wenyan Guo; Yali Huang; Wenjing Wang; Mimi Wan; Chun Mao; Jian Shen

Nanomotor-based H2S donor with mitochondrial targeting function for treatment of Parkinson's disease

2024

Reduction of endogenous hydrogen sulfide (H2S) is considered to have an important impact on the progress of Parkinson's disease (PD), thus exogenous H2S supplementation is expected to become one of the key means to treat PD. However, at present, it is difficult for H2S donors to effectively penetrate the blood brain barrier (BBB), selectively release H2S in brain, and effectively target the mitochondria of neuron cells. Herein, we report a kind of nanomotor-based H2S 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 H2S 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 H2S, 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 H2S donor is expected to enrich the current types of H2S donors and provide new ideas for the treatment of PD.

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