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
- 来源:
- 关键词:AblationAdhesionsAffectAftercareAnatomyAnimal ModelBlood CirculationCell Surface ReceptorsCell surfaceCellsClinicalContraceptive AgentsDiseaseEncapsulatedEndometrialEndometriumEngineeringEtiologyExcisionExposure toFemale of child bearing ageFertilityFluorescenceFutureGoalsGrantGreater sac of peritoneumGrowth Factor ReceptorsGynecologicHumanHyaluronic AcidImageImage-Guided SurgeryKDR geneLaparoscopic Surgical ProceduresLegal patentLesionLightMacacaMacaca mulattaMagnetic Resonance ImagingMalignant NeoplasmsMammalian OviductsMediatingMedicalMenstruationMethodsModelingMusNo Evidence of DiseaseNormal tissue morphologyOperative Surgical ProceduresOutcomePainPatientsPelvic PainPeptidesPermeabilityPhototherapyPolymersRattusReagentRecurrenceReportingResidual stateRetrograde MenstruationSCID MiceSeedsSignal TransductionSiliconSiteSpecificitySumSurfaceSurgeonTechniquesTestingThermal Ablation TherapyTimeTissue GraftsTissuesUterine cavityUterusVisualizationWomanWorkXenograft procedureangiogenesisbasecancer cellcancer therapycaprolactonecombinatorialdesignendometriosisethylene glycolexperimental studyfertility improvementimprovedinnovationintravenous injectioniron oxide nanoparticlenanoparticlenanoparticle deliverynanoparticle exposurenanotechnology platformnear infrared dyenonhuman primateoperationovarian neoplasmoverexpressionparticlephotothermal therapyprocedure safetyreproductive tractsubfertilitysurgery outcometargeted agenttheoriestreatment choice
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:
子宫内膜异位症是一种疼痛的疾病,子宫内膜样组织在宫腔外形成病变。
流行的理论,桑普森假说,是子宫内膜碎片通过
建立输卵管病变。尽管最近在药物治疗方面取得了进展,但仍然没有治愈的方法
对于许多女性来说,疾病和手术切除病变仍然是一种选择。不幸的是,
子宫内膜异位症术后复发率高,需要多次手术和内科治疗
治疗。导致复发的因素包括进一步的逆行月经和播种以及
手术中遗漏的微小子宫内膜异位症残留物。术中视觉化
这些微小的病变给妇科外科医生带来了成像方面的挑战。我们的目标是减少
手术后病情复发。我们已经创造了一种纳米平台并申请了专利,这种平台可以
术前全身应用实时近红外(NIR)勾画未切除组织
术中用荧光消融,并用光热消融消除未切除的残留物。平台是
最初是为癌症治疗开发的,适用于子宫内膜异位症。试剂由近红外光谱组成
可生物降解聚乙二醇聚乙二醇b-聚(ɛ-C)包埋的硅萘菁染料
己内酯))纳米粒。在靶细胞内被激活之前,这些颗粒是非荧光的。在……里面
初步研究,我们评估了近红外试剂在猕猴子宫内膜异位症移植到重度
联合免疫缺陷(SCID)小鼠。我们报告说,我们目前开发的纳米颗粒内化在
猕猴异位内膜细胞,并在小鼠的病变中产生近红外荧光信号。近红外光谱
治疗还消融了子宫内膜异位移植物。我们的前提是纳米颗粒平台辅助
外科技术可以应用于临床,以实现术中可视化和消除
未切除的子宫内膜异位症。在这项授权中,我们建议我们现有平台的特殊性可以是
通过靶向子宫内膜异位症病变中的细胞表面受体而增强。这一改进是必不可少的一步。
创造新的外科技术,评估手术的安全性,并进行有效的
未来的实验。在特定的目标1中,我们将合成靶向血管内皮生长因子受体2的聚合物纳米颗粒。
(KDR)或其他细胞表面部分在子宫内膜异位症中过度表达;评估人类细胞和
将该试剂与我们目前在猕猴组织中的平台进行比较。在具体目标2中,我们将验证新的
靶向药物可以全身注射,然后在人体皮损中特异性积聚。
靶向近红外治疗可导致异种移植物的光热消融。旧世界
非人灵长类动物,包括猕猴,会发生自发性子宫内膜异位症,并为
创造新的外科技术。为了推进这一模式,在具体目标3中,我们将把我们的研究扩展到测试
基于纳米颗粒的猕猴异位内膜消融术。
项目成果
期刊论文数量(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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