Nanomedicine-based anti-neuroinflammation strategy has become a promising dawn of Parkinson’s disease (PD) treatment. However, there are significant gaps in our understanding of the therapeutic mechanisms of antioxidant nanomedicines concerning the pathways traversing the blood-brain barrier (BBB) and subsequent inflammation mitigation. Here, we report nanozyme-integrated metal-organic frameworks with excellent antioxidant activity and chiral-dependent BBB transendocytosis as anti-neuroinflammatory agents for the treatment of PD. These chiral nanozymes are synthesized by embedding ultra-small platinum nanozymes (Ptzymes) into L-chiral and D-chiral imidazolate zeolite frameworks (Ptzyme@L-ZIF and Ptzyme@D-ZIF). Compared to Ptzyme@L-ZIF, Ptzyme@D-ZIF shows higher accumulation in the brains of male PD mouse models due to longer plasma residence time and more pathways to traverse BBB, including clathrin-mediated and caveolae-mediated endocytosis. These factors contribute to the superior therapeutic efficacy of Ptzyme@D-ZIF in reducing behavioral disorders and pathological changes. Bioinformatics and biochemical analyses suggest that Ptzyme@D-ZIF inhibits neuroinflammation-induced apoptosis and ferroptosis in damaged neurons. The research uncovers the biodistribution, metabolic variances, and therapeutic outcomes of nanozymes-integrated chiral ZIF platforms, providing possibilities for devising anti-PD drugs.

Tumor hypoxia compromises the effects of photodynamic therapy that consumes oxygen in the therapeutic process. Herein, a platinum (Pt)-carbon-integrated nanozyme with favorable catalase-like activity and photosensitizing properties was successfully constructed by immobilizing an ultrasmall Pt nanozyme into a MOF-derived carbon nanozyme through an in situ reduction strategy. The integration of a Pt nanozyme significantly improves the catalase activity of a carbon nanozyme that can effectively catalyze the decomposition of endogenous hydrogen peroxide to produce oxygen to improve the effects of photodynamic therapy. In addition, the integration of a Pt nanozyme also enhances the intrinsic photothermal performance of a carbon nanozyme. Combining the improved catalase-like activity with the enhanced photothermal properties together, the Pt-carbon nanozyme exhibits remarkable tumor inhibition ability in vivo. Thus, utilizing the enzymatic activity and photothermal/photosensitizing properties of nanozymes has great potential to overcome the limitations of traditional therapeutic strategies, and could inspire new directions for nanozyme-based biomedical applications.

Iron-based nanozymes, recognized for their biocompatibility and peroxidase-like activities, hold promise as catalysts in tumor therapy. However, their concurrent catalase-like activity undermines therapeutic efficacy by converting hydrogen peroxide in tumor tissues into oxygen, thus diminishing hydroxyl radical production. Addressing this challenge, this study introduces the hemin–cysteine–Fe (HCFe) nanozyme, which exhibits exclusive peroxidase-like activity. Constructed through a supramolecular assembly approach involving Fmoc-l-cysteine, heme, and Fe²⁺ coordination, HCFe distinctly incorporates heme and [Fe–S] within its active center. Sulfur coordination to the central Fe atom of Hemin is crucial in modulating the catalytic preference of the HCFe nanozyme towards peroxidase-like activity. This unique mechanism distinguishes HCFe from other bifunctional iron-based nanozymes, enhancing its catalytic selectivity even beyond that of natural peroxidases. This selective activity allows HCFe to significantly elevate ROS production and exert cytotoxic effects, especially against cisplatin-resistant esophageal squamous cell carcinoma (ESCC) cells and their xenografts in female mice when combined with cisplatin. These findings underscore HCFe’s potential as a crucial component in multimodal cancer therapy, notably in augmenting chemotherapy efficacy.

Reactive oxygen species (ROS), in moderate amounts, play an essential role in regulating different physiological functions in organisms. However, increased amounts of ROS may cause oxidative stress and damage to biomolecules, leading to a variety of diseases including inflammation and even cancer. Therefore, ROS scavenging reagents are needed to maintain healthy levels of ROS. With considerable advances in nanotechnology, nanozymes possess SOD or CAT-like activities with outstanding free radical scavenging activity, facile synthesis conditions, and excellent biocompatibility. Based on these extraordinary properties, nanozymes has been used to modulate the redox homeostasis and relieve the ROS-related injury. This has led to the emergence of nanozyme-based therapies. In the current review, we presented recently developed applications of nanozymes to treat ROS-dependent disorders with an emphasis on inflammatory and brain diseases.