Development of anti-inflammatory nanodrug for endometriosis treatment

项目摘要 子宫内膜异位症影响10%-15%的育龄妇女，发病率增加到50%-60%。 患有慢性盆腔疼痛和不孕不育。目前的治疗方法包括手术切除病变或激素治疗。 抑制；然而，这些可能有许多副作用和复发的高风险。精准靶向治疗 使用非激素类药物可成功根除子宫内膜异位症病变并缓解疼痛症状 降低其脱靶毒性。PSTAT3信号在免疫抑制和炎症反应中起关键作用 子宫内膜异位症。一种潜在的治疗方法是下调子宫内膜异位症的特异性 使用抗氧化剂的炎症。氧化铈纳米颗粒(纳米氧化铯)是一种有效的STAT3抑制剂 它们的抗炎和免疫调节作用。小尺寸的纳米陶瓷可以在 子宫内膜异位症通过通透性、血管生成的子宫内膜血管外渗造成的病变。我们的 初步结果显示，pSTAT3过表达导致雌激素依赖性炎症 我们的ROS清除纳米细胞显著减少了子宫内膜异位症病变的数量。 一只老鼠模型。包被白蛋白并与近红外荧光偶联的纳米粒(纳米氧化钙) 染料(吲哚青绿)，在光声图像下显示成功的系统性子宫内膜组织靶向 指导。我们假设这种新的纳米片(白蛋白-纳米钙-ICG)将显著抑制 子宫内膜异位病变的生长和结果减轻疼痛和不孕症。多模式成像同时提供 实时监测活体动物子宫内膜异位症进展及妊娠和胎儿发育。目标 1将研究pSTAT3在子宫内膜异位症中如何导致炎症和免疫抑制状态。 使用我们的子宫内膜异位症小鼠模型和体内成像。目标2将评估鼻咽癌的治疗潜力 纳米氧化钙对子宫内膜异位症进展和缓解疼痛的影响。Aim 3研究了纳米地毯是否会 提高生育力、子宫内膜容受性和着床能力。拟议的研究将支持揭示 子宫内膜异位症炎症的分子机制，导致非手术和非激素治疗。

Project Summary Endometriosis affects 10-15% of women of reproductive age, and the incidence increases to 50-60% in women with chronic pelvic pain and infertility. The current treatments include surgical removal of lesions or hormonal suppression; however, these may have many side effects and high risks of relapse. Precision-targeted therapy with a non-hormonal drug can successfully eradicate endometriosis lesions and alleviate pain symptoms while reducing its off-target toxicity. pSTAT3 signaling plays a crucial role in immunosuppression and inflammation in endometriosis. A potential therapeutic approach then is to downregulate the endometriosis-specific inflammation using antioxidant drugs. Cerium oxide nanoparticles (nanoceria) are potent STAT3 inhibitors due to their anti-inflammatory and immunomodulatory effects. The small-sized nanoceria can accumulate in endometriotic lesions by extravasation through permeable, angiogenic endometrial vasculature. Our preliminary results demonstrated pSTAT3 overexpression leads to estrogen-dependent inflammation in endometriosis, and our ROS scavenging nanoceria remarkably reduces the number of endometriotic lesions in a mouse model. The nanodrug (nanoceria), coated with albumin protein and conjugated with NIR fluorescent dye (indocyanine green), shows successful systemic endometrial tissue targeting under photoacoustic image guidance. We hypothesize the novel nanodrug (albumin-nanoceria-ICG) will significantly suppress endometriotic lesion growth and result in reduced pain and infertility. Multimodal imaging simultaneously offers real-time monitoring of endometriosis progression and pregnancy and fetal development in living animals. Aim 1 will investigate how pSTAT3 in endometriosis contributes to inflammatory and immunosuppressive conditions using our endometriosis mouse model and in vivo imaging. Aim 2 will evaluate the theranostic potential of nanoceria on endometriosis progression and pain alleviation. Aim 3 examines whether the nanodrug will improve fertility, endometrial receptivity, and implantation. The proposed studies will support uncovering the molecular mechanism of inflammation in endometriosis and lead to non-surgical and non-hormonal treatment.