Antioxidant and Anti-Inflammatory Potential of Platinum Nanozymes

Central Nervous System (CNS) diseases are one of the major burdens on our society and the search for effective treatments is increasingly difficult, due to their high incidence and complex etiology, which includes oxidative stress. Hence, many drawbacks are associated with molecular and enzymatic antioxidant therapies, but nanotechnology offers very powerful tools, represented by nanozymes, which can mimic the activity of the intracellular antioxidant enzymes and can counteract the excessive ROS accumulation characterising brain’s disorders. Among various materials, Platinum Nanoparticles (PtNPs) have shown unique multiple catalytic activities and high in vitro performances, which have been in part investigated within our research group in the last few years. This work aims at investigating the mechanism of oxidative stress rescue in the neurovascular unit (NVU) cells using a variety of nanozymes, including a detailed study of PtNP cellular trafficking and mechanism of action, as well as an examination of PtNP potential anti-inflammatory activity. In general, the catalytic activity of nanozymes is influenced by parameters such as size and shape. Additionally, the protein coating, naturally occurring when NPs come into contact with complex biological fluids, known as "biomolecular corona" (BMC), decreased the catalytic activity of PtNPs, while it increased NPs stability in culture media and promoted the uptake of NPs by cells. In this regard, we explored how the catalytic activity of PtNPs changed in different biological environments and the initially switched-off catalytic activity in the extracellular space was completely recovered and boosted after PtNPs internalization within lysosomes. Moreover, PtNPs efficiently reduced chemically induced ROS levels in primary neurons, primary astrocytes, and endhotelial cells, restoring the cellular physiological homeostasis. In addition, we demonstrated that intravitreal injections of PtNPs were able to recover the photoreceptor damage in an in vivo model of Age-Related Macular Degeneration (AMD), together with a reduction of retinal inflammation. This evidence led us to investigate the possible anti-inflammatory role of PtNPs both in the intra- and extracellular environment. Our preliminary results, concerning the PtNP-inhibited cellular migration toward pro- inflammatory stimuli (in vitro effect), and the BMC enrichment with pro-inflammatory molecules (cytokines), confirmed the possible medical application of PtNPs as antioxidant and anti-inflammatory agents for neurological diseases.