Development of anti-inflammatory nanodrug for endometriosis treatment

开发治疗子宫内膜异位症的抗炎纳米药物

基本信息

批准号：
10709492
负责人：
Jae-Wook Jeong
金额：
$ 62.86万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-30 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10709492
关键词：
Affect Age Albumins Animal Model Animals Anti-Inflammatory Agents Antioxidants Contrast Media Development Diagnosis Disease Elements Endometrial Enzymes Estrogens Excision Extravasation Fetal Development Fluorescent Dyes Functional disorder Goals Growth Hormonal Hormones Human Immunosuppression Incidence Indocyanine Green Infertility Inflammation Inflammatory Injections Lesion Macrophage Mediating Medical Medicine Menstrual cycle Modeling Molecular Multimodal Imaging Non-Steroidal Anti-Inflammatory Agents Operative Surgical Procedures Optics Pain Permeability Peroxidases Pharmaceutical Preparations Phenotype Phosphorylation Play Pregnancy Process Proteins Recurrent disease Reporting Risk Role Signal Transduction Stat3 protein Therapeutic Therapeutic Effect Tissues Toxic effect Woman angiogenesis catalase cerium oxide nanoparticle chronic pelvic pain endometriosis endometriosis-related infertility eutopic endometrium fertility improvement high risk human tissue image guided immunoregulation implantation improved in vivo imaging inhibitor innovation insight mineralization mouse model nano nanodrug nanoparticle nanosized novel novel strategies overexpression pain reduction pain relief pain symptom photoacoustic imaging pre-clinical real time monitoring reduce symptoms relapse risk reproductive side effect targeted delivery targeted treatment theranostics therapeutic evaluation tool

项目摘要

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.

项目概要子宫内膜异位症影响育龄妇女的10-15%，女性发病率增至50-60% 患有慢性盆腔疼痛和不孕症。目前的治疗方法包括手术切除病灶或激素治疗抑制;然而，这些可能有许多副作用和复发的高风险。精准靶向治疗用非激素药物可以成功根除子宫内膜异位病灶并缓解疼痛症状，同时减少其脱靶毒性。 pSTAT3 信号在免疫抑制和炎症中发挥着至关重要的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特异性的使用抗氧化药物治疗炎症。氧化铈纳米粒子 (nanoceria) 是有效的 STAT3 抑制剂，因为其抗炎和免疫调节作用。小尺寸的纳米陶瓷可以积聚在通过可渗透的、血管生成的子宫内膜脉管系统外渗引起的子宫内膜异位病变。我们的初步结果表明 pSTAT3 过度表达导致雌激素依赖性炎症子宫内膜异位症，我们的 ROS 清除纳米陶瓷显着减少了子宫内膜异位病变的数量鼠标模型。纳米药物（nanoceria），涂有白蛋白并与近红外荧光缀合染料（吲哚菁绿），在光声图像下显示成功的全身子宫内膜组织靶向指导。我们假设新型纳米药物（白蛋白-nanoceria-ICG）将显着抑制子宫内膜异位病变生长并导致疼痛和不孕症减轻。多模态成像同时提供实时监测活体动物的子宫内膜异位症进展以及妊娠和胎儿发育。目的 1 将研究子宫内膜异位症中的 pSTAT3 如何导致炎症和免疫抑制病症使用我们的子宫内膜异位症小鼠模型和体内成像。目标 2 将评估治疗诊断潜力 Nanoceria 对子宫内膜异位症进展和缓解疼痛的影响。目标 3 检查纳米药物是否会改善生育能力、子宫内膜容受性和植入。拟议的研究将支持揭示子宫内膜异位症炎症的分子机制并导致非手术和非激素治疗。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Exosome-Coated Prussian Blue Nanoparticles for Specific Targeting and Treatment of Glioblastoma.

外泌体包被的普鲁士蓝纳米颗粒用于胶质母细胞瘤的特异性靶向和治疗。

DOI：
10.1021/acsami.4c02364
发表时间：
2024-04-10
期刊：
ACS applied materials & interfaces
影响因子：
9.5
作者：
Meghan L Hill;Seock;Hyun;Cho Rong Park;Kay Hadrick;Md Nafiujjaman;Panangattukara Prabhakaran Praveen Kumar;Leila Mwangi;Rachna Parikh;Taeho Kim
通讯作者：
Taeho Kim

Europium-Doped Calcium Silicate Nanoparticles as High-Quantum-Yield Red-Emitting Phosphors.

掺铕硅酸钙纳米粒子作为高量子产红光荧光粉。