Ultra-bright fluorescent nanoparticles for colorectal adenoma detection

用于结直肠腺瘤检测的超亮荧光纳米颗粒

基本信息

批准号：
10456824
负责人：
Jatin Roper
金额：
$ 20.3万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-27 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10456824
关键词：
3-Dimensional APC gene Acetates Benign Binding Biopsy Specimen Cancer Etiology Carcinoma Cecum Cellulose Clinical Trials Colon Colonic Adenoma Colonoscopy Colorectal Colorectal Adenoma Colorectal Cancer Conjugating Agent Contrast Media Data Detection Development Diagnosis Environment Excision FOLR1 gene Family Fluorescence Folic Acid Future Goals Gold Human Hyaluronic Acid In Vitro Knowledge Left Lesion Light Malignant Neoplasms Methods Mucous Membrane Mus Mutation Normal tissue morphology Optics Organoids Pathologic Patients Physicians Polyethylene Glycols Polypectomy Polyps Precancerous Polyp Production Quantum Dots Reporting Risk Safety Sampling Sensitivity and Specificity Serrated Adenoma Side Surface Technology Testing Tissues Topical application Training Tubular Adenoma Tumor Suppressor Genes United States University Hospitals Villous Adenoma Visualization WNT Signaling Pathway Withdrawal adenoma base cancer diagnosis clinical application cohort colorectal cancer prevention colorectal cancer screening cost efficacy evaluation efficacy study improved mortality mouse model nanoparticle novel novel strategies overexpression particle premalignant screening targeted agent translational study tumor

项目摘要

Abstract Colorectal cancer is the 3rd leading cause of cancer-related mortality. Colorectal cancer screening significantly reduces cancer mortality through the detection of precancerous adenomas and removal with colonoscopy polypectomy. Inspection of the colon upon withdrawal from the cecum during colonoscopy is the most common method of adenoma detection in the United States. However, substantial evidence suggests that there are significant limitations to colonoscopy for adenoma detection due to inadequate visualization of polyps. Therefore, we recently developed ultrabright fluorescent nanoparticles (CA-dots) to highlight adenomas, and thereby, facilitate their detection. In our preliminary study, we showed that these nanoparticles preferentially bind to mouse colon adenomas and human adenoma organoids (i.e., mini-guts grown in three- dimensional environment). In this proposal, we hypothesize that CA-dots conjugated to folate groups will discriminate between adenoma and normal colon derived from colonoscopy subjects with high sensitivity and specificity. In Specific Aim 1, we will synthesize CA-dots for targeting of human adenomas. The goal of this aim is to prepare ultrabright fluorescent nanoparticles composed of cellulose acetate that demonstrate the highest accuracy in identification of colorectal adenomas. In Specific Aim 2, we will determine the efficacy of targeting fluorescent nanoparticles (CA-dots) to visually distinguish adenoma of various types from normal colon tissue. Here, we will study the efficacy of our CA-dot functionalized with folic acid to distinguish adenoma tissue from normal colon tissue biopsy specimens derived from a cohort of subjects who are referred to Duke University Hospital for removal of large (> 2 cm) adenomas. The goal of this proposal is to demonstrate efficacy of our novel fluorescent nanoparticles, CA-dots, to discriminate colon adenoma from normal colon ex vivo. Results from this study will provide preliminary data for R01-level applications to examine the application of this technology for the detection of precancerous adenomas during screening colonoscopy, which is our overarching goal.

抽象的结直肠癌是癌症相关死亡的第三大原因。结直肠癌筛查显着通过结肠镜检查检测癌前腺瘤并切除，降低癌症死亡率息肉切除术。在结肠镜检查期间从盲肠撤出结肠时对结肠的检查是最重要的美国常用的腺瘤检测方法。然而，大量证据表明由于结肠镜检查的可视化不足，腺瘤检测存在很大的局限性。息肉。因此，我们最近开发了超亮荧光纳米粒子（CA-dots）来突出显示腺瘤，从而促进其检测。在我们的初步研究中，我们表明这些纳米颗粒优先与小鼠结肠腺瘤和人类腺瘤类器官（即在三层中生长的迷你肠道）结合维度环境）。在此提案中，我们假设与叶酸基团缀合的 CA 点将以高灵敏度区分源自结肠镜检查受试者的腺瘤和正常结肠特异性。在具体目标 1 中，我们将合成用于靶向人类腺瘤的 CA 点。这个目标的目的是制备由醋酸纤维素组成的超亮荧光纳米粒子，其表现出最高的结直肠腺瘤鉴别的准确性。在具体目标 2 中，我们将确定目标的有效性荧光纳米颗粒（CA 点）可在视觉上区分各种类型的腺瘤与正常结肠组织。在这里，我们将研究用叶酸功能化的 CA 点区分腺瘤组织和正常结肠组织活检标本取自杜克大学的一组受试者医院切除大（> 2厘米）腺瘤。该提案的目标是证明我们的有效性新型荧光纳米颗粒 CA 点可在体外区分结肠腺瘤和正常结肠。结果本研究将为R01级应用提供初步数据，以检验本研究的应用在筛查结肠镜检查期间检测癌前腺瘤的技术，这是我们的总体目标。