Ultra-bright fluorescent nanoparticles for colorectal adenoma detection

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 通过检测癌前期腺瘤和结肠镜下切除降低癌症死亡率 息肉切除术。在结肠镜检查中，从盲肠取出时检查结肠最多 美国常见的腺瘤检测方法。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，因为结肠镜对腺瘤的可视化不足。 息肉。因此，我们最近开发了超亮荧光纳米颗粒(CA-DOTS)来突出 腺瘤，因此，有助于他们的发现。在我们的初步研究中，我们发现这些纳米颗粒 优先与小鼠结肠腺瘤和人腺瘤类器官结合(即，生长在三种环境中的迷你肠道) 空间环境)。在这项提议中，我们假设与叶酸基团连接的CA-DOTS将 结肠镜检查对腺瘤和正常结肠的鉴别诊断 专一性。在特定的目标1中，我们将合成针对人腺瘤的CA-Dot。这一目标的目标是 是制备由醋酸纤维素组成的超亮荧光纳米颗粒，展示了最高的 结直肠腺瘤诊断的准确性。在具体目标2中，我们将确定靶向的效力 荧光纳米粒子(CA-DOTS)用于从视觉上区分不同类型的腺瘤和正常结肠组织。 在这里，我们将研究我们的叶酸功能化的CA-Dot区分腺瘤组织和 来自杜克大学的一组受试者的正常结肠组织活检标本 医院切除大型(&gt；2厘米)腺瘤。这项提议的目的是证明我们的 新型荧光纳米粒子CA-DOTS用于体外区分结肠腺瘤和正常结肠腺瘤。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 在筛查结肠镜检查中检测癌前病变的技术，这是我们的 首要目标。

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.