生物可解离铂量子点簇纳米酶通过微环境重塑实现非激素性子宫内膜异位症治疗
Bio-dissociable platinum quantum dot cluster nanozymes for nonhormonal endometriosis therapy through microenvironment remodeling
摘要
该研究构建生物可解离铂量子点簇(PtQDC)纳米酶,用于非激素性子宫内膜异位症(EMS)治疗。PtQDC在病灶组织液中逐步解离,持续清除活性氧和活性氮,使异位内膜细胞脱离有利氧化还原窗口,导致能量代谢受损、线粒体功能障碍和凋亡。小鼠EMS模型中,PtQDC减少病灶数量和体积,重塑腹腔微环境,抑制病理性血管生成并减轻疼痛相关信号;同时降低促炎因子、升高IL-10、调节巨噬细胞表型。RNA-seq显示Ptgs2、Mmp3和Postn下调。结果表明PtQDC整合抗氧化、抗炎、抗纤维化和抗血管生成活性,是多靶点非激素治疗EMS的潜在策略。
原文摘要
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.
推荐理由:提出可解离铂量子点簇纳米酶这一非激素多靶点策略,并在小鼠模型中结合微环境、疼痛和转录组验证,对子宫内膜异位症相关不孕研究有参考价值;但尚缺临床与更完整方法学信息。
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