Antioxidant lipoic acid ligand-shell gold nanoconjugates against oxidative stress caused by α-synuclein aggregates

Gold nanoparticles are becoming a promising platform for the delivery of drugs to treat neurodegenerative diseases. Parkinson's disease, associated with the aggregation of α-synuclein, is a condition that results in dysfunctional neuronal cells leading to their degeneration and death. Oxidative stress has been strongly implicated as a common feature in this process. The limited efficacy of the traditional therapies and the development of associated severe side effects present an unmet need for preventive and adjuvant therapies. The organosulfur compound lipoic acid, naturally located in the mitochondria, plays a powerful antioxidative role against oxidative stress. However, the efficacy is limited by its low physiological concentration, and the administration is affected by its short half-life and bioavailability due to hepatic degradation. Here we exploited the drug delivery potential of gold nanoparticles to assemble lipoic acid, and administered the system into SH-SY5Y cells, a cellular model commonly used to study Parkinson's disease. We tested the nanoconjugates of GNPs-LA, under an oxidative environment induced by gold nanoparticle/α-synuclein conjugates (GNPs-α-Syn). GNPs-LA were found to be biocompatible and capable of restoring the cell damage caused by high-level reactive oxygen species generated by excessive oxidative stress in the cellular environment. We conclude that GNPs-LA may serve as promising drug delivery vehicles conveying antioxidant molecules for the treatment of Parkinson's disease.