Engineering modified manganese dioxide nanozymes with neuroprotective properties for potential stroke therapy

We developed lactoferrin (Lf)-coated MnO 2 nanozymes loaded with insoluble resveratrol (RVL) to enhance blood-brain barrier (BBB) penetration and targeted drug delivery. The MnO 2 @RVL@Lf nanozymes (20–60 nm) exhibited drug-loading efficiency of 52.4% in 40 μg∙mL -1 RVL concentrations, controlled RVL release (69.8% under hypoxia), and oxygen generation (10.1 mg∙mL -1 ). In vivo studies demonstrated reduced brain malondialdehyde (16.56 vs. 21.30 for RVL alone) without systemic toxicity, as evidenced by stable liver/kidney enzymes [Lactate dehydrogenase (LDH), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and Alkaline phosphatase (ALP)] and preserved organ histology. The nanozymes also downregulated pro-inflammatory factors [Tumor necrosis factor-alpha (TNF-α), Interleukin-2 beta (IL-2β), Matrix metalloproteinase-9 (MMP-9)] while upregulating anti-inflammatory IL-10, promoting neuroregeneration. Improved motor function, learning, and reduced cerebral edema further confirmed therapeutic efficacy. Overall, MnO 2 @RVL@Lf nanozymes mitigate ischemic stroke damage by combating oxidative stress, suppressing inflammation, and protecting neurons, highlighting their potential for stroke therapy.