Multifunctional Carbon-Dot-Photosensitizer Nanoassemblies for Inhibiting Amyloid Aggregates, Suppressing Microbial Infection, and Overcoming the Blood-Brain Barrier.

Amyloid aggregation, microbial infection, and the blood-brain barrier (BBB) are considered critical obstructions for the treatment of Alzheimer's disease (AD). At present, existing treatment strategies are rarely able to overcome these critical factors. Herein, we propose an innovative treatment strategy and design multifunctional nanoassemblies (yCDs-Ce6) from coassembling photosensitizers (chlorine e6) and yellow fluorescent carbon dots, which endow yCDs-Ce6 with the functions for photodynamic and photothermal therapy (PDT and PTT). Compared with reported inhibitors, yCDs-Ce6 can suppress amyloid aggregation for 7 days, disaggregate aggregates, reduce amyloid aggregation-induced cytotoxicity, and prevent microbial growth by PDT and PTT. Moreover, yCDs-Ce6 can specifically target amyloid aggregates and visually label amyloid aggregates. yCDs-Ce6 can also cross the BBB upon near-infrared light irradiation and clear amyloid deposition in APP/PS1 mice by PDT and PTT. Meanwhile, yCDs-Ce6 did not cause significant negative effects on normal cells or tissues. Based on the methods of PPT and PTT treatment, the research deeply explores the effect of the novel nanoassemblies on two hypotheses of AD, opening a novel therapeutic paradigm for research amyloid-related diseases.