Dual-Carbon Dots Composite: A Multifunctional Photo-Propelled Nanomotor Against Alzheimer's β-Amyloid

The abnormal accumulation of β-amyloid protein (Aβ) is considered as the main pathological hallmark of Alzheimer's disease (AD). The design of potent multifunctional theranostic agents targeting Aβ is one of the effective strategies for AD prevention and treatment. Nanomotors as intelligent, advanced, and multifunctional nanoplatforms can perform many complex tasks, but their application in AD theranostics is rare. Herein, sub-10nm multifunctional dual-carbon dots composites (ERCD) with photo-propelled nanomotor behavior are fabricated by conjugating near-infrared (NIR) carbon dots (RCD) of thermogenic and photodynamic capability with the previously reported epigallocatechin gallate-derived carbonized polymer dots (ECD). ERCD-1 (ECD:RCD = 1:2.5) showed potent inhibitory capability similar to ECD in the absence of NIR light, and exhibited photooxygenation activity and nanomotor behavior powered by "self-thermophoretic force" under NIR irradiation, significantly enhancing the inhibition, disaggregation, and photooxygenation capabilities. The nanomotor suppressed Aβ fibrillization and rapidly disaggregated mature Aβ fibrils at very low concentrations (0.5 µg mL⁻¹). Moreover, the NIR-activated ERCD-1 imaged Aβ plaques in vivo and prolonged nematode lifespan by 6 d at 2 µg mL⁻¹. As a proof-of-concept, this work opened a new avenue to the design of multifunctional sub-10nm nanomotors targeting Aβ for AD theranostics.