Liu Wenwen, Shen Jie, You Jiaqi, Wang Tao, Yang Pusheng, Miao Yaxin, Peng Xiaotong, Yu Yimin, Liu Chengyu, Li Ang, Sun Jing
The Gynecology Department, Shanghai Key Laboratory of Maternal-Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
Mater Today Bio. 2025 Jul 1;33:102041. doi: 10.1016/j.mtbio.2025.102041. eCollection 2025 Aug.
Endometriosis, an estrogen-dependent inflammatory disorder prevalent in reproductive-age women, is characterized by the growth of endometrial-like tissue outside the uterine cavity, leading to chronic pain and infertility. Current therapeutic strategies primarily focus on lesion removal and pain alleviation, often at the cost of compromising ovarian function and natural conception. Herein, we engineered a nanocomposite with polydopamine and dydrogesterone for precise and gentle endometriosis treatment while protecting ovarian function and fertility. It combines polydopamine 's anti-inflammatory and antioxidant capacities with dydrogesterone's ectopic lesion regression capability while maintaining physiological ovulation. To enhance the lesion-specific delivery, the nanocomposite was functionalized with polyethylene glycol and laminin. Through in vitro and in vivo studies, we demonstrate that the nanocomposites exhibit potent antioxidant and anti-inflammatory properties, coupled with targeted delivery to ectopic endometrial cells. The nanocomposites effectively accumulate in ectopic lesions, modulate macrophage polarization, and promote the atrophy and clearance of ectopic endometrial tissue. Importantly, this therapeutic approach preserves ovarian reserve function and fertility, showing no significant adverse effects on ovarian health. In summary, we present an innovation non-surgical therapeutic strategy for endometriosis that demonstrates both safety and efficacy while preserving ovarian reserve function and fertility potential.
子宫内膜异位症是一种在育龄女性中普遍存在的雌激素依赖性炎症性疾病，其特征是子宫腔外出现类似子宫内膜的组织生长，导致慢性疼痛和不孕。目前的治疗策略主要集中在病灶切除和疼痛缓解上，往往以损害卵巢功能和自然受孕能力为代价。在此，我们设计了一种由聚多巴胺和地屈孕酮组成的纳米复合材料，用于精确、温和地治疗子宫内膜异位症，同时保护卵巢功能和生育能力。它将聚多巴胺的抗炎和抗氧化能力与地屈孕酮的异位病灶消退能力相结合，同时维持生理性排卵。为了增强病灶特异性递送，该纳米复合材料用聚乙二醇和层粘连蛋白进行了功能化修饰。通过体外和体内研究，我们证明该纳米复合材料具有强大的抗氧化和抗炎特性，并能靶向递送至异位子宫内膜细胞。纳米复合材料有效地积聚在异位病灶中，调节巨噬细胞极化，并促进异位子宫内膜组织的萎缩和清除。重要的是，这种治疗方法保留了卵巢储备功能和生育能力，对卵巢健康没有明显的不良影响。总之，我们提出了一种创新的非手术治疗子宫内膜异位症的策略，该策略在保留卵巢储备功能和生育潜力的同时，兼具安全性和有效性。
