Reshaping the oxidative stress microenvironment by bionic chiral Cu–Phe (d/l) nanozymes for promoting osteoimmunomodulation and osteogenic differentiation

Abstract

Inflammatory bone defects pose a serious threat to human health and traditional stem cell therapies exhibit limited efficacy in addressing the high oxidative stress environment associated with such defects. Inspired by the response mechanism of the intracellular antioxidant defense system (IADS), we propose a metal–organic framework (MOF) nanozyme that mimics the structure of deep-sea lobster hemocyanin and found that its simulated activity of superoxide dismutase (SOD) and catalase (CAT) can be regulated through a chiral engineering strategy. By utilizing different chiral phenylalanine ligands, we rationally prepared Cu–Phe (D/L) (where D represents right-handed and L represents left-handed) nanozymes. Taking the optimal nanozyme as an example, studies show that Cu–Phe (L) can effectively clear ROS, protect and maintain broad cellular functionality in an oxidative stress microenvironment, and regulate the macrophage phenotype. We believe that the development of Cu–Phe (L) nanozymes based on a chiral molecule-dependent strategy can effectively reshape the oxidative stress microenvironment, enhance osteoimmune modulation, and promote stem cell osteogenic differentiation. The meticulously designed chiral Cu–Phe (D/L) provide instructive insights for the rational construction of MOF nanozymes and the treatment of inflammatory defects.