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

Abstract BackgroundMitochondrial 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.MethodsWe use hyaluronic acid nanoparticles (HA-NPs) of different molecular weights to protect the mitochondria and salvages the mild and limited damage in mitochondria. Our HA-NPs with 2,190 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, we use NPs with ubiquitin specific peptidase 30 (USP30) siRNA to promote mitophagy. Meanwhile, by adding PINK1 antibodies, our NPs can selectively target the irreversibly damaged mitochondria, preventing the excessive clearance of healthy mitochondria.ResultsOur HA-NPs with 2,190 kDa HA can protect the mitochondria and salvage the mitochondrial function of the mild and limited damage conditions in both SH-SY5Y cells and PINK1 knockout MEF cells. NPs with USP30 siRNA and PINK1 antibodies can selectively target and promote the clearance of irreversibly damaged mitochondria both in vitro and in vivo .ConclusionsWe successfully designed and developed NPs for the treatment of PD that can target different stages of mitochondrial damage. This strategy is expected to overcome the problems associated with the excessive clearance of healthy mitochondria and has great potential for clinical applications. Our study provides a novel strategy for PD treatment.