Bio-dissociable platinum quantum dot cluster nanozymes for nonhormonal endometriosis therapy through microenvironment remodeling

Endometriosis (EMS) is a chronic inflammatory disorder marked by ectopic endometrial lesions that commonly cause pain and infertility. Existing surgical and hormonal therapies are limited by adverse effects and high recurrence rates, while nanozyme-based approaches offer opportunities to develop alternative therapeutic strategies. Here, we developed bio-dissociable platinum quantum dot clusters (PtQDC) as nanozymes for nonhormonal EMS therapy. PtQDC undergoes gradual dissociation in lesion tissue fluid and exhibits sustained scavenging activity toward reactive oxygen and nitrogen species. The resulting shift of endometriotic cells from their highly oxidative state beyond a favorable redox window was accompanied by impaired energy metabolism, mitochondrial dysfunction, and apoptosis. In the mouse model of EMS, PtQDC reduced lesion number and volume, remodeled the peritoneal microenvironment, inhibited pathological angiogenesis, and attenuated pain-associated signaling. PtQDC also reduced proinflammatory factors, increased IL-10, and modulated macrophage phenotypic profiles. RNA-seq analysis further revealed downregulation of Ptgs2, Mmp3, and Postn, genes associated with inflammation, invasion, and fibrosis. Thus, PtQDC integrates antioxidant, anti-inflammatory, antifibrotic, and antiangiogenic activities as a potential multitarget nonhormonal therapy for EMS.