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

• 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
• 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

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.

摘要 结直肠癌是癌症相关死亡的第三大原因。结直肠癌筛查显著 通过检测癌前腺瘤和结肠镜切除降低癌症死亡率 息肉切除术在结肠镜检查过程中，从盲肠撤出后对结肠的检查是最重要的。 在美国腺瘤检测的常用方法。然而，大量证据表明， 结肠镜检查对腺瘤的检测有很大的局限性， 息肉因此，我们最近开发了超亮荧光纳米颗粒（CA点），以突出 腺瘤，从而促进它们的检测。在我们的初步研究中，我们发现这些纳米颗粒 优先结合小鼠结肠腺瘤和人腺瘤类器官（即，迷你肠生长在三个- 环境）。在这个提议中，我们假设与叶酸基团缀合的CA-点将 以高灵敏度区分来自结肠镜检查对象的腺瘤和正常结肠， 的特异性在具体目标1中，我们将合成用于靶向人类腺瘤的CA点。这一目标的目的 是制备由醋酸纤维素组成的超亮荧光纳米颗粒， 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 使用荧光纳米颗粒（CA点）来在视觉上区分各种类型的腺瘤与正常结肠组织。 在这里，我们将研究我们的叶酸功能化的CA点区分腺瘤组织和 正常结肠组织活检标本，来源于转诊至杜克大学的受试者队列 医院切除大（> 2 cm）腺瘤。本提案的目的是证明我们的 新的荧光纳米颗粒，CA点，以区别结肠腺瘤从正常结肠离体。结果 本研究将为R 01级应用程序提供初步数据，以检查此 在结肠镜检查中检测癌前腺瘤的技术，这是我们的 总体目标。