Ultrabright Theranostic SERRS Nanoparticles for Gastrointestinal Endoscopy

用于胃肠内窥镜检查的超亮治疗诊断 SERRS 纳米颗粒

• 批准号: 10461094
• 负责人: Stephan Rogalla
• 金额: $ 64.22万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10461094
• 关键词: Ablation; Adverse effects; Animal Model; Animal Testing; Animals; Biodistribution; Biomedical Engineering; Cancer Etiology; Cancerous; Cause of Death; Cessation of life; Chemistry; Classification; Clinical; Clinical Trials; Colon; Colon Carcinoma; Colonoscopy; Colorectal; Colorectal Cancer; Crows; Data; Detection; Doctor of Philosophy; Dose; Early Diagnosis; Endoscopes; Endoscopy; Ensure; Esophagus; Evaluation; Eye; Feces; Fingerprint; Food; Formulation; Gastroenterology; Gastrointestinal Endoscopy; Generations; Gold; Grant; Histologic; Home; Human; Image; Intestines; Laboratories; Lasers; Lesion; Lesion by Morphology; Light; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of esophagus; Malignant neoplasm of gastrointestinal tract; Memorial Sloan-Kettering Cancer Center; Methods; Microscopic; Mind; Molecular; Morphology; Mus; Nanotechnology; Oncology; Organ; Outcome; Pathology; Patient-Focused Outcomes; Photons; Positron-Emission Tomography; Precancerous Polyp; Preparation; Prognosis; Radiology Specialty; Raman Spectrum Analysis; Rectum; Research; Signal Transduction; Silicon Dioxide; Specificity; Stomach; Surface; Techniques; Technology; Testing; Toxic effect; Translating; United States; United States National Institutes of Health; Validation; Woman; base; cancer type; care outcomes; clinical care; clinical practice; clinical translation; design; detection limit; dosage; experimental study; gastrointestinal; imaging agent; in vivo; innovation; intravenous injection; malignant stomach neoplasm; men; molecular imaging; nanoparticle; novel; novel strategies; photothermal therapy; premalignant; screening; theranostics; uptake

Summary Gastrointestinal cancers such as esophageal, gastric, and colorectal cancers represent some of the most challenging and lethal cancer types. Colorectal cancer alone is the third most common cause of cancer in men and women in the United States, despite implementation of colonoscopy for early detection. Esophageal and gastric cancers are less common, but their prognosis is dire if not detected early. The current standard of clinical practice uses conventional white light endoscopy, which is limited in that it offers only morphological information, has difficulties detecting microscopic lesions, and is highly operator dependent. Much greater benefits of upper and lower endoscopy would be anticipated if it would rely on specific molecular signals. To this end, we have developed a new generation of ultra-sensitive Raman nanoparticle beacons – 4th generation SERRS-Nanostars (4G Nanostars) – that after intravenous injection home specifically to both precancerous and cancerous lesions. They emit a unique Raman spectroscopic signature (“Raman fingerprint”) that clearly identifies the intestinal lesion. Because of the very high sensitivity (limit of detection in the attomolar range), even microscopic lesions of 100 µm in size can be detected. The 4G- Nanostars were developed with a special eye towards clinical translation, and consist of inert materials. Importantly, a clinical Raman endoscope that can detect the 4G-Nanostars has already been developed. We will first characterize the 4G-Nanostars with the assistance of the NIH Nanotechnology Characterization Laboratory to ensure optimal formulation and exclude any unexpected adverse effects ahead of in vivo studies. We will then determine optimal dosage in mice, and use non-invasive dynamic positron emission tomography imaging to quantify the biodistribution of 4G-Nanostars in organs and intestinal lesions. 4G-Nanostar uptake into esophageal, gastric and colonic lesions will be quantified and ranked according to the histological classification of each lesion, in order to determine if they can be used to noninvasively discriminate different lesion types. Subsequently, we will determine the accuracy with which 4G-Nanostars can detect the intestinal lesions in both mouse and large animal models of esophageal, gastric and colon cancer. We will test the accuracy of 4G-Nanostar imaging using a clinical Raman endoscope developed by our collaborators. We will also evaluate the use of SERRS-Nanostars as a theranostic agent using photothermal ablation. In summary, this proposal aims to establish a fundamentally new and highly translatable method that will allow more sensitive and specific detection and ablation of both (pre-)malignant lesions of the esophagus, stomach, colon and rectum. The experiments are designed thoroughly and rigorously so that at the end of the grant period all data has been acquired to file an IND for a clinical trial.

概括 食管，胃和有色癌等胃肠癌癌 具有挑战性和致命的癌症类型。仅结直肠癌是男性癌症的第三大原因 以及美国的妇女，进行结肠镜检查目的地进行早期检测。食管和 胃癌不太常见，但是如果未发现，它们的预后是可怕的。 当前的临床实践标准使用常规的白光内窥镜检查，这是有限的 仅提供形态学信息，难以检测微观病变，并且是高度操作员 依赖。上层和下部镜面的好处会更大的好处，如果它会依靠 特定的分子信号。为此，我们开发了新一代的超敏感拉曼 纳米颗粒信标 - 第四代锯齿纳米级（4G纳米纳斯塔尔） - 静脉注射后 专门针对癌前病变和取消病变的家园。他们散发出独特的拉曼光谱镜 签名（“拉曼指纹”）清楚地识别出肠道病变。由于敏感性很高 （在大气压范围内的检测极限），甚至可以检测到100 µm的显微病变。 4G- 纳米级是针对临床翻译的特殊眼光，由惰性材料组成。 重要的是，已经开发了一种可以检测4G纳米施患者的临床拉曼内窥镜。 我们将在NIH纳米技术表征的帮助下首先将4G纳米级 实验室确保最佳公式并在体内研究之前排除任何意外的不良影响。 然后，我们将确定小鼠的最佳剂量，并使用非侵入性动态正电子发射断层扫描 成像以量化器官和肠道病变中4G纳米级的生物分布。 4G纳米级吸收 根据组织学对食道，胃病变和结肠病变进行量化和排名 每个病变的分类，以确定它们是否可以用于非侵入性区分不同 病变类型。随后，我们将确定4G纳米船员可以检测到肠道的准确性 小鼠和大型动物模型的食管，胃癌和结肠癌的病变。我们将测试 使用我们的合作者开发的临床拉曼内窥镜的4G纳米级成像的准确性。我们将 还可以评估使用光热消融的SERRS-NANOSTAR作为溶剂剂。总之， 该提案旨在建立一种根本新的，高度翻译的方法，该方法将允许更多 对食管，胃，颜色的两种（前）恶性病变的敏感和特异性检测和消融 和直肠。实验的设计彻底，严格，以便在赠款期结束时全部设计 已获得数据以提交临床试验的IND。