Elongated nanoporous Au networks improve somatic cell direct conversion into induced dopaminergic neurons for Parkinson's disease therapy

Abstract

The efficient production of dopaminergic neurons via the direct conversion of other cell types is of inter-est as a potential therapeutic approach for Parkinson's disease. This study aimed to investigate the use of elongated porous gold nanorods (AuNpRs) as an enhancer of cell fate conversion. We observed that AuNpRs promoted the direct conversion of fibroblasts into dopaminergic neurons in vivo and in vitro. The extent of conversion of fibroblasts into dopaminergic neurons depended on the porosity of AuNpRs, as determined by their aspect ratio. The mechanism underlying these results involves specific AuNpR-induced transcriptional changes that altered the expression of antioxidant-related molecules. The gener-ation of dopaminergic neurons via the direct conversion method will open a new avenue for developing a therapeutic platform for Parkinson's disease treatment.Statement of significance In this study, we applied modified gold nanoporous materials (AuNpRs) to the direct lineage reprogram-ming of dopaminergic neurons. The cell reprogramming process is energy-intensive, resulting in an ex-cess of oxidative stress. AuNpRs facilitated the direct conversion of dopaminergic neurons by ameliorat-ing oxidative stress during the reprogramming process. We have found this mechanistic clue from high throughput studies in this research work.(c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.