A nanoparticle-based approach for surgical imaging and intraoperative treatment of endometriosis

基于纳米颗粒的子宫内膜异位症手术成像和术中治疗方法

基本信息

  • 批准号:
    9893322
  • 负责人:
  • 金额:
    $ 26.26万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-02-20 至 2022-01-31
  • 项目状态:
    已结题

项目摘要

Project Summary/ Abstract: Endometriosis is a painful disorder where endometrium-like tissue forms lesions outside of the uterine cavity. The prevalent theory, the Sampson Hypothesis, is that endometrial fragments pass [retrograde] through the fallopian tube to establish the lesions. Despite recent advances in medical therapy, there remains no cure for the disease and surgical removal of the lesions remains a choice for many women. Unfortunately, the recurrence rate for endometriosis after surgery is high with patients requiring multiple operations and medical treatment. Factors contributing to recurrence include further retrograde menstruation and seeding as well as the presence of minute endometriotic residues that are missed during surgery. Intraoperative visualization of these minute lesions poses an imaging challenge for gynecologic surgeons. Our goal is to reduce recurrence of the disease after surgery. We have created and patented a nanoplatform that can be administered systemically before surgery to delineate unresected tissue with real-time near infrared (NIR) fluorescence during surgery and eliminate unresected residues with photothermal ablation. The platform was originally developed for cancer therapy and is applicable to endometriosis. The reagent consists of the NIR dye, silicon naphthalocyanine (SiNc) encapsulated in biodegradable PEG-PCL (poly (ethylene glycol)-b-poly(ɛ- caprolactone)) nanoparticles. The particles are non-fluorescent until activated within the target cells. In preliminary studies, we assessed the NIR reagent in macaque endometriotic tissue grafted into severe combined immunodeficient (SCID) mice. We reported that our currently developed nanoparticles internalized in macaque endometriotic cells and generated a NIR fluorescence signal in lesions in the mice. The NIR treatment also ablated the endometriotic grafts. Our premise is that nanoparticle platform-assisted surgical techniques can be employed clinically to permit intraoperative visualization and elimination of the unresected endometriosis. In this grant, we propose that the specificity of our existing platform can be enhanced by targeting cell surface receptors in endometriotic lesions. This refinement is an essential step towards creating new surgical techniques, assessing the safety of the procedures, and conducting impactful future experiments. In specific aim 1, we will synthesize polymeric nanoparticles that target VEGF receptor 2 (KDR), or other cell surface moieties, overexpressed in endometriosis; assess the particles in human cells and compare the reagent to our current platform in macaque tissue. In specific aim 2 we will validate that the new targeted agent can be injected systemically and then specifically accumulate in human lesions engrafted into SCID mice, and that targeted NIR treatment results in photothermal ablation of the xenografts. Old-World nonhuman primates, including macaques develop spontaneous endometriosis and provide an animal model for creating new surgical techniques. To advance this model, in specific aim 3 we will extend our studies to test nanoparticle-based ablation of ectopic endometrium in macaques.
项目摘要/摘要:

项目成果

期刊论文数量(0)
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科研奖励数量(0)
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{{ truncateString('OV D SLAYDEN', 18)}}的其他基金

Imaging and treatment of endometriosis in nonhuman primates
非人灵长类动物子宫内膜异位症的影像学和治疗
  • 批准号:
    10700030
  • 财政年份:
    2021
  • 资助金额:
    $ 26.26万
  • 项目类别:
Development of magnetic hyperthermia for the systemic treatment of endometriosis
磁热疗系统治疗子宫内膜异位症的进展
  • 批准号:
    10490250
  • 财政年份:
    2021
  • 资助金额:
    $ 26.26万
  • 项目类别:
Imaging and treatment of endometriosis in nonhuman primates
非人灵长类动物子宫内膜异位症的影像学和治疗
  • 批准号:
    10309094
  • 财政年份:
    2021
  • 资助金额:
    $ 26.26万
  • 项目类别:
Imaging and treatment of endometriosis in nonhuman primates
非人灵长类动物子宫内膜异位症的影像学和治疗
  • 批准号:
    10474484
  • 财政年份:
    2021
  • 资助金额:
    $ 26.26万
  • 项目类别:
A nanoparticle-based approach for surgical imaging and intraoperative treatment of endometriosis
基于纳米颗粒的子宫内膜异位症手术成像和术中治疗方法
  • 批准号:
    10112277
  • 财政年份:
    2020
  • 资助金额:
    $ 26.26万
  • 项目类别:
A macaque model for endometriosis induced pelvic pain and infertility
子宫内膜异位症引起的盆腔疼痛和不孕症的猕猴模型
  • 批准号:
    8512128
  • 财政年份:
    2013
  • 资助金额:
    $ 26.26万
  • 项目类别:
A macaque model for endometriosis induced pelvic pain and infertility
子宫内膜异位症引起的盆腔疼痛和不孕症的猕猴模型
  • 批准号:
    8666680
  • 财政年份:
    2013
  • 资助金额:
    $ 26.26万
  • 项目类别:
ANALYSIS OF RNA FROM ECTOPIC ENDOMETRIUM IN RHESUS MACAQUES
恒河猴异位子宫内膜 RNA 分析
  • 批准号:
    8357805
  • 财政年份:
    2011
  • 资助金额:
    $ 26.26万
  • 项目类别:
PRECLINICAL STUDIES ON HUMAN FIBROIDS IN IMMUNODEFICIENT MICE
免疫缺陷小鼠人体肌瘤的临床前研究
  • 批准号:
    8357768
  • 财政年份:
    2011
  • 资助金额:
    $ 26.26万
  • 项目类别:
SUPPRESSION OF MENSTRUAL BLEEDING IN RHESUS MACAQUES
抑制恒河猴的月经出血
  • 批准号:
    8357806
  • 财政年份:
    2011
  • 资助金额:
    $ 26.26万
  • 项目类别:

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