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

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL Bioactive Materials Pub Date : 2023-09-22 DOI:10.1016/j.bioactmat.2023.09.001

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

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Abstract

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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具有线粒体靶向功能的纳米马达H2S供体治疗帕金森病

内源性硫化氢（H2S）的减少被认为对帕金森病（PD）的进展有重要影响，因此外源性补充H2S有望成为治疗PD的关键手段之一。然而，目前H2S供体很难有效穿透血脑屏障（BBB），选择性释放脑内H2S，并有效靶向神经元细胞的线粒体。本文报道了一种基于纳米马达的H2S供体，它是由l-半胱氨酸衍生物修饰的聚乙二醇（PEG-Cys）和2-甲基丙烯酰氧基乙基磷酰胆碱（MPC）之间的自由基聚合反应获得的。这种H2S供体不仅能有效突破血脑屏障，而且能被脑PD位点神经元中的胱硫醚β-合成酶（CBS）和线粒体中的3-巯基丙酮酸硫转移酶（3-MST）特异性催化产生H2S，赋予其趋化/运动能力。此外，纳米马达独特的趋化作用可以实现精确靶向大脑和受损神经元细胞病变疾病的线粒体的目的。这种基于纳米马达的H2S供体有望丰富现有类型的H2S供体，并为PD的治疗提供新的思路。

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来源期刊

Bioactive Materials Biochemistry, Genetics and Molecular Biology-Biotechnology

CiteScore

28.00

自引率

6.30%

发文量

436

审稿时长

20 days

期刊介绍： Bioactive Materials is a peer-reviewed research publication that focuses on advancements in bioactive materials. The journal accepts research papers, reviews, and rapid communications in the field of next-generation biomaterials that interact with cells, tissues, and organs in various living organisms. The primary goal of Bioactive Materials is to promote the science and engineering of biomaterials that exhibit adaptiveness to the biological environment. These materials are specifically designed to stimulate or direct appropriate cell and tissue responses or regulate interactions with microorganisms. The journal covers a wide range of bioactive materials, including those that are engineered or designed in terms of their physical form (e.g. particulate, fiber), topology (e.g. porosity, surface roughness), or dimensions (ranging from macro to nano-scales). Contributions are sought from the following categories of bioactive materials: Bioactive metals and alloys Bioactive inorganics: ceramics, glasses, and carbon-based materials Bioactive polymers and gels Bioactive materials derived from natural sources Bioactive composites These materials find applications in human and veterinary medicine, such as implants, tissue engineering scaffolds, cell/drug/gene carriers, as well as imaging and sensing devices.