Abstract
Nickel has recently emerged as a promising catalytic center for single-atom catalysts, owing to its biological relevance, redox versatility, and favorable coordination chemistry. Herein, we report the synthesis of a multifunctional nanozyme (Ni/PEG-FA) comprising atomically dispersed nickel sites anchored on a nitrogen-doped carbon support. The nanozyme is functionalized with poly(ethylene glycol) to improve colloidal stability and biocompatibility, and further conjugated with folic acid to enable the selective targeting of cancer cells overexpressing folate receptors. Ni/PEG-FA exhibits dual enzyme-mimicking activity, catalyzing both peroxidase-like and superoxide dismutase-like reactions for efficient reactive oxygen species generation under physiological conditions. In addition, Ni/PEG-FA shows strong photothermal conversion upon near-infrared laser irradiation, enabling effective thermal ablation of tumor cells. In vitro and in vivo evaluations demonstrate that Ni/PEG-FA elicits synergistic antitumor effects by combining catalytic oxidative stress with photothermal therapy, with minimal systemic toxicity. These findings underscore the potential of Ni-based single-atom nanozymes as a safe and effective platform for reactive oxygen species-powered cancer therapy.