Modulation of copper-induced neurotoxicity by monoisoamyl 2,3-dimercaptosuccinic acid loaded nanoparticles through inhibition of mitophagy and reduction of oxidative stress in SH-SY5Y cells.

Copper (Cu) dysregulation, often stemming from ATP7B gene mutations, exacerbates neurological disorders like Huntington's, Alzheimer's, and Parkinson's diseases. Monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA) shows promise in mitigating Cu induced neurotoxicity by chelating intracellular Cu ions, reducing oxidative stress, and restoring antioxidant enzyme function. However, challenges such as poor bioavailability hinder its therapeutic efficacy. Nano-delivery systems offer a solution by improving MiADMSA's solubility, stability, and targeted delivery, potentially minimizing off-target effects. In this study, MiADMSA was loaded into a polymer conjugated with lipoic acid (LA) and human serum albumin (HSA) using a coacervation crosslinking method. The prepared nanoparticles were optimized using a Box-Behnken design. Evaluation in SH-SY5Y cells revealed promising neuroprotective effects against Cu induced neurotoxicity, highlighting the potential of MiADMSA-loaded nanocarriers as a therapeutic strategy for neurodegenerative diseases associated with metal dysregulation.