Polydopamine-Based Nanocomposite as a Biomimetic Antioxidant with a Variety of Enzymatic Activities for Parkinson’s Disease

Overproduction of reactive oxygen species (ROS) and cumulative oxidative stress induce the degeneration of neuromelanin-containing dopaminergic neurons in the substantia nigra pars compacta (SNpc) of PD patients. Due to its redox property, melanin-like polydopamine (PDA) has been studied for its ability to remove ROS with a series of antioxidant enzyme mimetic activities including superoxide dismutase (SOD) and catalase (CAT). Glutathione peroxidase (GPx) is important for maintaining ROS metabolic homeostasis, but only a few GPx-like nanozymes have been studied for in vivo therapy. As we know, selenocysteine is essential for the antioxidant activity of GPx. Hence, we co-synthesized PDA with selenocystine (SeCys) to prepare a nanocomposite (PDASeCys) with GPx-like activity. The results showed that the PDASeCys nanocomposite has the same CAT and SOD enzymatic activities as PDA but better free radical scavenging efficiency and additional GPx enzymatic activity than PDA. In the 1-methyl-4-phenyl-pyridine ion (MPP⁺)-induced PD cell model, PDASeCys could increase intracellular GPx levels effectively and protect SH-SY5Y neuronal cells from oxidative stress caused by MPP⁺. In vivo, the PDASeCys nanocomposite effectively inhibited 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium (MPTP)-induced Parkinson-related symptoms of mice when it was injected into the substantia nigra (SN). This polydopamine-based nanocomposite containing selenocystine with a variety of enzymatic activities including GPx-like activity synthesized by a one-pot method provides convenience and safety in the neuromelanin-like nanozyme-based therapeutic strategy for oxidative stress-induced PD.