Emerging Chiral Nanozymes: Enantioselective Catalysis and Biomedical Applications.

Chiral nanozymes are biomimetic materials that combine nanomaterials' unique physicochemical properties with enzyme-like catalytic functions. Their chiral microenvironments enable selective recognition and catalysis of substrate enantiomers, with demonstrated applications in biosensing, disease diagnosis/treatment, and antibacterial/anti-inflammatory therapies. This article provides a systematic review of the design and synthesis strategies, catalytic types, mechanisms of action, and biomedical application research progress of chiral nanozymes. In terms of design and synthesis, four strategies are emphasized, namely chiral ligand modification, the chiral template method, chiral self-assembly, and chiral defect engineering. In catalytic performance and mechanism, the redox activities such as peroxidase, oxidase, catalase, and superoxide dismutase, as well as esterase-/protease-like hydrolysis activity, were summarized. An in-depth exploration was conducted of the molecular mechanism by which chiral microenvironments synergistically regulate substrate binding and electron transfer through steric hindrance effects and multiple weak interactions. In addition, the latest research progress of chiral nanozymes in enantiomer recognition and detection, tumor chemodynamic/photodynamic/sonodynamic combination therapy, neurodegenerative disease protein aggregation intervention, and selective antibacterial and inflammatory regulation is also reviewed. Finally, the challenges and future development directions faced by chiral nanozymes in precise regulation of catalytic selectivity, long-term biological safety in vivo, and clinical translation are discussed. STATEMENT OF SIGNIFICANCE: 1. Four strategies for constructing chiral nanozymes: ligand modification, template induction, self-assembly, and defect engineering. 2. Mechanistic insights into how chiral microenvironments regulate oxidoreductase-like and hydrolase-like catalysis. 3. Biomedical applications, including chiral biosensing, tumor therapy, neurodegenerative disease intervention, and antibacterial treatment. 4. Critical evaluation of chiral-induced spin selectivity (CISS), the hurdles to clinical translation, and future directions for the intelligent design of chiral nanozymes.