BBB-permeable carbon dots ameliorate Alzheimer's-like phenotypes in mice by suppressing oxidative stress, neuroinflammation, and amyloid-β aggregation.

Alzheimer's disease (AD) is a common neurodegenerative disorder wherein reactive oxygen species (ROS) and Amyloid-β-protein (Aβ) play critical roles. Inspired by traditional Chinese charcoal drug and the anti-inflammatory properties of some carbon dots, we developed Radix Isatidis derived carbon dots (RI-CDs) via a hydrothermal method. The RI-CDs can cross the blood-brain barrier (BBB) and were thus evaluated for AD therapy. In vitro, RI-CDs scavenged ROS, inhibited Aβ42 aggregation, protected SH-SY5Y cells, and regulated inflammatory factors. In AD mice, the Morris water maze test and nesting experiment demonstrated that RI-CDs improved the learning and memory ability of mice and improved their nesting ability. Importantly, RI-CDs reduced ROS/Aβ42 in the hippocampus of AD mice, downregulated NLRP3 pathway-related cellular inflammatory factors, and upregulated the expression of BDNF/SYN/PSD95, thereby restoring damaged neurons. These findings demonstrate the compelling neuroprotective efficacy of RI-CDs, highlighting their potential as a promising therapeutic agent for AD.