Ectopic Endometrium-Targeted M1 Macrophage-Derived Nanovesicles for Treatment of Endometriosis

Abstract

Endometriosis (EMs) is a common gynecological disorder in women of reproductive age, often presenting with pelvic pain and infertility. Its progression is closely linked to estrogen levels. While hormonal therapies are effective, long-term use can disrupt systemic hormone balance. To address this, we developed M1 macrophage membrane-derived nanovesicles (M1NVs) that leverage the natural CCL2-CCR2 targeting axis to selectively deliver drugs to ectopic endometrial lesions. The estrogen receptor antagonist bazedoxifene (BAZ) was encapsulated into M1NVs, enabling targeted delivery to ectopic tissue following systemic administration. This approach locally antagonizes estrogen signaling, resulting in effective attenuation of inflammatory infiltration, suppression of angiogenesis, and reduction of fibrosis, thereby inhibiting the growth of ectopic endometrial tissue. Importantly, it did not adversely affect ovarian or uterine structure and function. This strategy offers a targeted and efficient alternative for the treatment of endometriosis.