{"paper_id":"9432e05d-f612-4d2a-86b9-1a4ad491b4eb","body_text":"Clinically Validated Leptin Receptor as a Target for Liposomal Delivery of Metformin in Endometriosis TherapyClick to copy article linkArticle link copied!\n- Yunyu XuYunyu XuDepartment of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei 230022, Anhui, ChinaNHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No. 81 Meishan Road, Hefei 230032, Anhui, ChinaEngineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No. 81 Meishan Road, Hefei 230032, Anhui, ChinaMore by Yunyu Xu\n- Youyan FangYouyan FangDepartment of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei 230022, Anhui, ChinaNHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No. 81 Meishan Road, Hefei 230032, Anhui, ChinaEngineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No. 81 Meishan Road, Hefei 230032, Anhui, ChinaMore by Youyan Fang\n- Yue WangYue WangDepartment of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei 230022, Anhui, ChinaNHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No. 81 Meishan Road, Hefei 230032, Anhui, ChinaEngineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No. 81 Meishan Road, Hefei 230032, Anhui, ChinaMore by Yue Wang\n- Rong WuRong WuDepartment of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei 230022, Anhui, ChinaNHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No. 81 Meishan Road, Hefei 230032, Anhui, ChinaEngineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No. 81 Meishan Road, Hefei 230032, Anhui, ChinaMore by Rong Wu\n- Mengni ZhouMengni ZhouDepartment of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei 230022, Anhui, ChinaNHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No. 81 Meishan Road, Hefei 230032, Anhui, ChinaEngineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No. 81 Meishan Road, Hefei 230032, Anhui, ChinaMore by Mengni Zhou\n- Pengcheng LuPengcheng LuDepartment of Anesthesiology, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, Anhui, ChinaMore by Pengcheng Lu\n- Ying WangYing WangDepartment of Anesthesiology, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, Anhui, ChinaMore by Ying Wang\n- Ye HeYe HeDepartment of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei 230022, Anhui, ChinaNHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No. 81 Meishan Road, Hefei 230032, Anhui, ChinaEngineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No. 81 Meishan Road, Hefei 230032, Anhui, ChinaMore by Ye He\n- Jiqian Zhang*Jiqian Zhang*Email: [email protected]Department of Anesthesiology, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, Anhui, ChinaMore by Jiqian Zhang\n- Zhaolian Wei*Zhaolian Wei*Email: [email protected]Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei 230022, Anhui, ChinaNHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No. 81 Meishan Road, Hefei 230032, Anhui, ChinaEngineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No. 81 Meishan Road, Hefei 230032, Anhui, ChinaMore by Zhaolian Wei\n- Shasha Zhu*Shasha Zhu*Email: [email protected]Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei 230022, Anhui, ChinaNHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No. 81 Meishan Road, Hefei 230032, Anhui, ChinaEngineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No. 81 Meishan Road, Hefei 230032, Anhui, ChinaMore by Shasha Zhu\nAbstract\nEndometriosis is a common, estrogen-driven chronic gynecologic disorder defined by the ectopic growth of endometrial-like tissue within the peritoneal cavity. Existing treatment options, primarily surgery and hormonal therapy, are limited by inconsistent efficacy and treatment-related adverse effects. A major challenge in developing effective therapies is the lack of drug delivery strategies that specifically target ectopic lesions. In this study, we demonstrate through clinical analyses that the leptin receptor (LEPR) is strongly associated with endometriosis and that its expression is independent of age, menstrual cycle phase, pelvic pain, infertility history, and disease stage. Leveraging this insight, we designed a liposomal delivery platform (HLipo) modified with the HY7 peptide to target LEPR, enabling highly specific delivery to ectopic lesions in a mouse model. Notably, LEPR blockade or mutation abolished this lesion-specific accumulation, further supporting the LEPR-dependent targeting of HLipo. Building on this platform, we developed Met@HLipo, a metformin-loaded formulation that exhibited markedly superior antiendometriotic efficacy compared with free metformin, without detectable toxicity. Mechanistically, our study identifies a therapeutic mechanism whereby Met@HLipo induces autophagy-mediated degradation of estrogen receptor β (ERβ), thereby directly targeting a central driver of endometriosis pathogenesis. These findings highlight a clinically validated molecular target and present a highly translational, nonhormonal, and nonsurgical therapeutic strategy for endometriosis.\nCited By\nThis article has not yet been cited by other publications.\nArticle Views\nAltmetric\nCitations\nArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. 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