Photomodulating Carbon Dots for Spatiotemporal Suppression of Alzheimer's β-Amyloid Aggregation

Extracellular deposition of beta-amyloid (A beta) peptide aggregates is a major characteristic of Alzheimer's disease (AD) brain. Because A beta peptide aggregates aggravate neuropathy and cognitive impairment for AD patients, numerous efforts have been devoted to suppressing A beta self-assembly as a prospective AD treatment option. Here, we report A beta-targeting, red-light-responsive carbon dots (CDs), and their therapeutic functions as a light-powered nanomodulator to spatiotemporally suppress toxic A beta aggregation both in vitro and in vivo. Our aptamer-functionalized carbon dots (Apta@ CDs) showed strong targeting ability toward A beta(42) species. Moreover, red LED irradiation induced Apta@CDs to irreversibly denature A beta peptides, impeding the formation of beta-sheet-rich A beta aggregates and attenuating A beta-associated cytotoxicity. Consequently, Apta@CDs-mediated photomodualtion modality achieved effective suppression of A beta aggregation in vivo, which significantly reduced the A beta burden at the targeted sites in the brain of 5xFAD mice by similar to 40% and similar to 25% according to imaging and ELISA analyses, respectively. Our work demonstrates the therapeutic potential of photomodulating CDs for light-driven suppression against A beta self-assembly and related neurotoxicity.