Near-infrared enhanced organic se-doped carbon nitride quantum dots nanozymes as SOD/CAT mimics for anti-Parkinson via ROS-NF-κB-NLRP3 inflammasome axis

Abstract

Development of effective and innovative approaches by inhibiting chronic microglial neuroinflammationto degrade α-synuclein is urgent for Parkinson’s disease (PD) treatment. Here, organic Se(−2 valence)-doped carbon nitride quantum dots (SegCN-QDs) nanozyme were prepared for selective gas/drug combination therapy of PD. SegCN-QDs nanozyme could load Cordycepin (Cor) to cross the blood–brain barrier (BBB) for visualized targeted regulation of microglia to efficiently scavenge α-synuclein aggregates to treat PD. We revealed that SegCN-QDs could targete microglia through the specific interactions between the V domain of the positively charged advanced glycation end products (RAGE) on the surface of microglia and the negatively charged SegCN-QDs. SegCN-QDs also exhibited a wide absorption band spanning entire visible and even near-infrared (NIR) regions, enabling the promotion of water splitting to generate oxygen through NIR irradiation. In addition, SegCN-QDs showed superoxide dismutase (SOD)/catalase (CAT) mimics enzyme activities, which converted reactive oxygen species (ROS) into O2 to alleviate inflammatory response by inhibiting the ROS-nuclear factor-kappa B (NF-κB)/NOD-like receptor protein 3 (NLRP3) axis at the PD sites. Furthermore, the produced oxygen, scavenged ROS, and the delivered Cor were proved to successfully decrease α-synuclein to mitigate dopaminergic neuron injury in vivo and improved motor dysfunction and exploration ability of MPTP-induced PD mice.