Extracellular deposition of β-amyloid (Aβ) peptide aggregates is a major characteristic of Alzheimer's disease (AD) brain. Because Aβ peptide aggregates aggravate neuropathy and cognitive impairment for AD patients, numerous efforts have been devoted to suppressing Aβ self-assembly as a prospective AD treatment option. Here, we report Aβ-targeting, red-light-responsive carbon dots (CDs), and their therapeutic functions as a light-powered nanomodulator to spatiotemporally suppress toxic Aβ aggregation both in vitro and in vivo. Our aptamer-functionalized carbon dots (Apta@CDs) showed strong targeting ability toward Aβ42 species. Moreover, red LED irradiation induced Apta@CDs to irreversibly denature Aβ peptides, impeding the formation of β-sheet-rich Aβ aggregates and attenuating Aβ-associated cytotoxicity. Consequently, Apta@CDs-mediated photomodualtion modality achieved effective suppression of Aβ aggregation in vivo, which significantly reduced the Aβ burden at the targeted sites in the brain of 5xFAD mice by ∼40% and ∼25% according to imaging and ELISA analyses, respectively. Our work demonstrates the therapeutic potential of photomodulating CDs for light-driven suppression against Aβ self-assembly and related neurotoxicity.
Keywords: Alzheimer’s disease; amyloid self-assembly; aptamer; carbon dot; photonic nanoagent.