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.

Chemiexcitation-Triggered Photosensitizer Activation for Photooxidation of Aβ1–42 Aggregates

“…The photosensitizer diagnostic agents for photooxidation of Aβ aggregates reported mainly include organic small molecules, organometallic complexes, metal–organic frameworks, carbon-based nanomaterials, and bio-organic materials. − The organic photosensitizer thioflavin T (ThT) can be excited at 442 nm, which transfers energy to the ground state molecular oxygen, resulting in the production of singlet oxygen ( 1 O 2 ) . This in turn leads to the depolymerization of Aβ aggregates.…”