Enzyme-mimetic nanodots catalytically alleviate stress-induced hypertension via anti-neuroinflammation effects

Stress-induced hypertension (SIH), driven by reactive oxygen/nitrogen species (ROS/RNS) accumulation and neuroinflammation in the rostral ventrolateral medulla (RVLM), lacks effective targeted therapies. Here, we synthesize ultrasmall manganese-doped carbon dots (Mn@CDs) (~ 2.5 nm) with multienzyme-mimetic activities, including superoxide dismutase, catalase, and peroxidase. Mn@CDs enable effective scavenging of diverse types of ROS/RNS, thereby protecting rat neuroblastoma B104 and microglial GMI-R1 cells from H₂O₂-induced damage. Mn@CDs treatment also suppresses the cell apoptosis (via regulating Bcl-2/Bax and cleaved caspase-3) and reduce pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) of GMI-R1 cells. In SIH rats, injection of Mn@CDs into RVLM normalizes arterial/systolic/diastolic blood pressure and renal sympathetic nerve activity. Mechanistically, Mn@CDs downregulate NOX2/NOX4 within RVLM region and alleviate oxidative stress, thus reversing microglial activation and reducing neuronal apoptosis. This work presents a non-pharmaceutical catalytic strategy based on biocompatible Mn@CDs nanozymes targeting the RVLM ROS-neuroinflammation axis for SIH.