A novel nanoparticle system targeting damaged mitochondria for the treatment of Parkinson's disease

Yue Chen; Bosong Zhang; Lina Yu; Jinyu Zhang; Yufang Zhao; Lifen Yao; Hongji Yan; Weiming Tian

doi:10.1016/j.bioadv.2022.212876

A novel nanoparticle system targeting damaged mitochondria for the treatment of Parkinson's disease

Biomater Adv. 2022 Jul:138:212876. doi: 10.1016/j.bioadv.2022.212876. Epub 2022 May 23.

Authors

Yue Chen¹, Bosong Zhang¹, Lina Yu¹, Jinyu Zhang¹, Yufang Zhao¹, Lifen Yao², Hongji Yan³, Weiming Tian⁴

Affiliations

¹ School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, People's Republic of China.
² Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150080, China.
³ Division of Glycoscience, Department of Chemistry, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH, Royal Institute of Technology, AlbaNova University Center, 106 91 Stockholm, Sweden; AIMES-Center for the Advancement of Integrated Medical and Engineering Sciences at Karolinska Institutet, KTH Royal Institute of Technology, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
⁴ School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, People's Republic of China. Electronic address: tianweiming@hit.edu.cn.

PMID: 35913233
DOI: 10.1016/j.bioadv.2022.212876

Abstract

Mitochondrial damage is one of the primary causes of neuronal cell death in Parkinson's disease (PD). In PD patients, the mitochondrial damage can be repaired or irreversible. Therefore, mitochondrial damage repair becomes a promising strategy for PD treatment. In this research, hyaluronic acid nanoparticles (HA-NPs) of different molecular weights are used to protect the mitochondria and salvage the mild and limited damage in mitochondria. The HA-NPs with 2190 k Dalton (kDa) HA can improve the mitochondrial function of SH-SY5Y cells and PTEN induced putative kinase 1 (PINK1) knockout mouse embryo fibroblast (MEF) cells. In cases of irreversible damage, NPs with ubiquitin specific peptidase 30 (USP30) siRNA are used to promote mitophagy. Meanwhile, by adding PINK1 antibodies, the NPs can selectively target the irreversibly damaged mitochondria, preventing the excessive clearance of healthy mitochondria.

Keywords: Hyaluronic acid; Nanoparticles; PINK1 antibody; Parkinson's disease; USP30 siRNA.

MeSH terms

Animals
Humans
Mice
Mitochondria / metabolism
Mitochondrial Proteins / genetics
Nanoparticles* / therapeutic use
Neuroblastoma* / metabolism
Parkinson Disease* / drug therapy
Protein Kinases / genetics
Thiolester Hydrolases / metabolism
Ubiquitin-Protein Ligases / genetics

Substances

Mitochondrial Proteins
Usp30 protein, human
Ubiquitin-Protein Ligases
Protein Kinases
Thiolester Hydrolases