Multifunctional carbon dots as a therapeutic nanoagent for modulating Cu(ii)-mediated -amyloid aggregation

Abstract

The abnormal self-assembly of cerebral -amyloid (A) peptides into toxic aggregates is a hallmark of Alzheimer's disease (AD). Here, we report on multifunctional carbon dots that can chelate Cu(ii) ions, suppress A aggregation, and photooxygenate A peptides. Copper ions have high relevance to AD pathogenesis, causing Cu(ii)-mediated A aggregation and oxidative damage to neuronal cells. For effective conjugation with Cu(ii)-bound A complexes, we have designed carbon dots that possess nitrogen (N)-containing polyaromatic functionalities on their surface by employing o-phenylenediamine (OPD) as a polymerization precursor. We demonstrate that the polymerized OPD (pOPD)-derived carbon dots exhibit multiple capabilities against Cu(ii)-mediated A aggregation. Furthermore, the pOPD-derived carbon dots exhibited dramatically enhanced absorption and fluorescence upon coordination with Cu(ii) ions and effectively photooxygenated A peptides. The photodynamically modulated A residues lost the propensity to coordinate with Cu(ii) and to assemble into toxic aggregates. This work demonstrates the potential of carbon dots as a multifunctional -sheet breaker and provides a promising anti-amyloidogenic strategy for future A-targeted AD treatments.