Polymeric Nanozyme with SOD Activity Capable of Inhibiting Self‐ and Metal‐Induced α‐Synuclein Aggregation

Despite decades of research, Parkinson's disease is still an idiopathic pathology for which no cure has yet been found. This is partly explained by the multifactorial character of most neurodegenerative syndromes, whose generation involves multiple pathogenic factors. In Parkinson's disease, two of the most important ones are the aggregation of alpha-synuclein and oxidative stress. In this work, we address both issues by synthesizing a multifunctional nanozyme based on grafting a pyridinophane ligand that can strongly coordinate CuII, onto biodegradable PEGylated polyester nanoparticles. The resulting nanozyme exhibits remarkable superoxide dismutase activity together with the ability to inhibit the self-induced aggregation of alpha-synuclein into amyloid-type fibrils. Furthermore, the combination of the chelator and the polymer produces a cooperative effect whereby the resulting nanozyme can also halve CuII-induced alpha-synuclein aggregation. A multifunctional polymeric nanozyme capable to strongly coordinate CuII is designed, generating complexes with a prominent superoxide dismutase activity. Moreover, the combination of the polymeric platform with the chelator allows the nanozyme to perform its second activity: inhibition of both the self- and metal-induced aggregation of alpha-synuclein peptides. image