Silicon-Carbon Dots-Loaded Mesoporous Silica Nanocomposites (mSiO2@SiCDs): An Efficient Dual Inhibitor of Cu2+-Mediated Oxidative Stress and Aβ Aggregation for Alzheimer's Disease

Abstract

The redox-active metal ions, especially Cu²⁺, are highly correlated to Alzheimer's disease (AD) by causing metal ion-mediated oxidative stress and toxic metal-bound β-amyloid (Aβ) aggregates. Numerous pieces of evidence have revealed that the regulation of metal homeostasis could be an effective therapeutic strategy for AD. Herein, in virtue of the interaction of both amino-containing silane and ethylenediaminetetraacetic acid disodium salt for Cu²⁺, the silicon-carbon dots (SiCDs) are deliberately prepared using these two raw materials as the cocarbon source; meanwhile, to realize the local enrichment of SiCDs and further maximize the chelating ability to Cu²⁺, the SiCDs are feasibly loaded to the biocompatible mesoporous silica nanoparticles (mSiO₂) with the interaction between residual silane groups on SiCDs and silanol groups of mSiO₂. Thus-obtained nanocomposites (i.e., mSiO₂@SiCDs) could serve as an efficient Cu²⁺ chelator with satisfactory metal selectivity and further modulate the enzymic activity of free Cu²⁺ and the Aβ₄₂-Cu²⁺ complex to alleviate the pathological oxidative stress with an anti-inflammatory effect. Besides, mSiO₂@SiCDs show an inspiring inhibitory effect on Cu²⁺-mediated Aβ aggregation and further protect the neural cells against the toxic Aβ₄₂-Cu²⁺ complex. Moreover, the transgenic Caenorhabditis elegans CL2120 assay demonstrates the protective efficacy of mSiO₂@SiCDs on Cu²⁺-mediated Aβ toxicity in vivo, indicating its potential for AD treatment.

Keywords: Alzheimer’s disease; Cu2+ chelation; mesoporous silica nanoparticles; silicon–carbon dots; β-amyloid.