Multimeric interacting interface of biologically synthesized zinc oxide nanoparticle corona efficiently sequesters α-synuclein against protein fibrillation.

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons along with the accumulation of amyloid plaques with alpha-synuclein (αS) as the major constituent. αS is an intrinsically disordered protein with the potential to undergo a cascade of structural transitions from a soluble disordered conformation to ordered cross-β-sheet-rich insoluble amyloid fibrils. Small molecules like polyphenols and peptides with anti-amyloidogenic potential can mitigate fibrillation in vitro but fail in vivo owing to poor bioavailability. To overcome this problem, a platform that simultaneously enhances the bioavailability of the mitigators and efficiently sequesters αS monomers against amyloidosis is needed. Accordingly, herein, the sequestering potential of surface-moderated zinc oxide nanoparticles was explored; in silico and in vitro studies showed that the moderated nano-interfaces efficiently sequestered αS in amorphous aggregates, which were termed as flocs. Moreover, GC-MS-based analysis of the bio-nano corona highlighted the rationale for efficient sequestering of αS monomers against amyloidosis by the biologically synthesized zinc oxide nanoparticle compared with other nanoparticle surfaces. Thus, this work exemplifies the multimeric interacting interface as a platform to efficiently sequester the αS protein and simultaneously enhance the bioavailability of the phytochemicals.