Neodymium‐Modified Molybdenum Blue Nanoclusters Alleviate Polycystic Ovary Syndrome via Radical Scavenging

Abstract Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. Chronic inflammation and oxidative stress are key contributors to its pathogenesis, yet effective and safe therapeutic strategies remain limited. In this study, a neodymium‐modified molybdenum blue (MoNd) nanocluster is evaluated as a therapeutic strategy for PCOS, featuring excellent biocompatibility and ROS scavenging capacity. In a DHEA‐induced PCOS mouse model, MoNd treatment significantly improved ovarian morphology, restored ovulatory function, and alleviated metabolic abnormalities. Metabolomic analysis indicated that MoNd nanoclusters significantly improved hepatic antioxidant capacity and redox balance. Transcriptomic analysis revealed that MoNd modulates key pathways associated with PCOS, particularly those related to oxidative stress and inflammation. Moreover, significant regulatory effects are observed on the PI3K‐AKT and p53 signaling pathways following MoNd treatment, which are implicated in cell death processes such as ferroptosis and cellular senescence, respectively. Specifically, MoNd nanoclusters effectively preserved granulosa cell viability by counteracting ROS‐induced ferroptotic and senescent responses, and attenuated the pro‐inflammatory polarization of macrophages. Collectively, the findings highlight MoNd nanocluster as a potent nanotherapeutic agent capable of ameliorating both reproductive and metabolic features of PCOS, paving the way for its future application in clinical interventions for PCOS.