Nanozymes are widely applied for treating various major diseases, including neurological diseases and tumors. However, the biodegradability of nanozymes remains a great challenge, which hinders their further clinical translation. Based on the microenvironment of osteoarthritis (OA), a representative pH‐responsive biodegradable hollow‐structured manganese Prussian blue nanozyme (HMPBzyme) is designed and applied for treatment of OA. HMPBzyme with good pH‐responsive biodegradability, biocompatibility, and multi‐enzyme activities is constructed by bovine serum albumin bubbles as a template‐mediated biomineralization strategy. HMPBzyme suppresses hypoxia‐inducible factor‐1α (HIF‐1α) expression and decreases reactive oxygen species (ROS) level in the in vitro experiment. Furthermore, HMPBzyme markedly suppresses the expression of ROS and alleviates the degeneration of cartilage in OA rat models. The results indicate that the biodegradable HMPBzyme inhibits oxidative damage and relieves hypoxia synergistically to suppress inflammation and promote the anabolism of cartilage extracellular matrix by protecting mitochondrial function and down‐regulating the expression of HIF‐1α, which modulates the phenotypic conversion of macrophages from pro‐inflammatory M1 subtype to anti‐inflammatory M2 subtype for OA treatment. This research lays a solid foundation for the design, construction, and biomedical application of biodegradable nanozymes and promotes the application of nanozymes in biomedicine.

Prussian Blue Nanoenzymes In article 2200787 by Rongxin He, Wei Gao, Xiaojun Cai and co‐workers, hollow Prussian blue nanozymes (HPBZs) significantly normalize the osteoporosis microenvironment, thereby inhibiting osteoclast formation and osteoclast resorption for treatment of osteoporosis, possibly owing to the suppression of the mitogen‐activated protein kinase and nuclear factor κB signaling pathways.

Osteoporosis (OP) is the most common orthopedic disease in the elderly and the main cause of age‐related mortality and disability. However, no satisfactory intervention is currently available in clinical practice. Thus, an effective therapy to prevent or delay the development of OP should be devised. Osteoclastogenesis overactivation and excessive bone resorption are the main characteristics of OP. Accordingly, a paradigm for nanozyme‐mediated normalization of the disease microenvironment to regulate osteoclast differentiation and delay OP is proposed. Hollow Prussian blue nanozymes (HPBZs) are prepared via template‐free hydrothermal synthesis and selected as representative nanozymes. The intrinsic osteoclast activity‐remodeling bioactivities of the HPBZs are explored in vitro and in vivo, focusing on their impact on osteogenesis and specific molecular mechanisms using an OP murine model. The HPBZs significantly normalize the OP microenvironment, thereby inhibiting osteoclast formation and osteoclast resorption, possibly owing to the suppression of intracellular reactive oxygen species generation, the mitogen‐activated protein kinase, and nuclear factor κB signaling pathways. Consistently, in an ovariectomy‐induced OP murine model, HPBZ treatment significantly attenuates osteoporotic bone loss in vivo. The findings confirm the HPBZ‐mediated normalization of the disease microenvironment for the treatment of OP and suggest its application to other inflammation‐related diseases.