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Molecular Contrast Agents Based on Gold Nanocages for OCT Imaging of Cancer

基于金纳米笼的分子造影剂用于癌症 OCT 成像

基本信息

批准号：
7650112
负责人：
Xingde Li
金额：
$ 28.27万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-01 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7650112
关键词：
Acids Algorithms Animal Model Antibodies Biomedical Engineering Biomedical Technology Biopsy Blinded Cancer Model Carcinoma Cell surface Cheek structure Chemistry Clinical Contrast Media Detection Diagnostic Dysplasia Esophagectomy Excision Exhibits Extracellular Matrix Gold Hamsters Histology Human Image Imaging technology Inherited Length Malignant Neoplasms Measures Medicine Metaplasia Microanatomy Molecular Neoplasm Metastasis Neoplasms Normal tissue morphology Optical Biopsy Optical Coherence Tomography Optics Organ Pathology Patients Production Property Reaction Research Personnel Resolution Sampling Errors Screening for cancer Series Silver Specificity Specimen Spectrum Analysis Survival Rate System Techniques Time Tissues Topical application Treatment outcome Universities Washington absorption antibody conjugate base cancer diagnosis cancer imaging cancer surgery carcinogenesis experience improved in vivo interest molecular recognition multidisciplinary nano nanoparticle novel optical imaging programs scale up success

项目摘要

DESCRIPTION (provided by applicant): This proposal is a multidisciplinary program involving researchers from the Departments of Bioengineering, Chemistry, Pathology and Medicine at the University of Washington. The objective is to develop and validate a new class of molecular nano contrast agents based on biocojugatible gold nanocages for improving the ability of optical coherence tomography (OCT) in early cancer detection. Cancers develop over a period of several years and experience molecular and structural changes prior to metastasis. Early cancer detection remains a critical clinical objective to improve survival rates and treatment outcomes. OCT is a recently developed non-invasive technique that can perform "optical biopsy" by cross-sectional imaging of tissue microanatomy in vivo and in real time. OCT offers excellent spatial resolution; however, currently it has limited success in early cancer detection mainly because of the weak intrinsic optical contrast between normal tissue and early cancer and its lack of molecular specificity. The hypothesis of this proposal is that novel molecular contrast agents can enhance OCT imaging contrast and molecular specificity for early cancer detection. Unlike other metallic nanoparticles, gold nanocages exhibit very strong, tunable optical resonance in the near infrared range while remaining a small size (35-65 nm). Gold nanocages can provide both intensity and spectroscopic contrast enhancement for OCT imaging and they permit facile conjugation of molecular recognition agents for targeting. The specific aims are to: (1) develop gold nanocages with strong absorption or scattering in the near-infrared range using galvanic replacement nanochemistry and optimize synthesis conditions for scaling-up production; (2) characterize the optical properties of nanocages, compare the results with theoretical calculations based on discrete dipole approximation, and quantify intensity and spectroscopic OCT contrast enhancement; (3) perform in vivo animal model studies to quantitatively evaluate the ability of OCT for early cancer detection with assistance of bioconjugated nanocages; and (4) investigate the ability of OCT in detecting dysplasia and early cancer on human esophagectomy specimens using molecular contrast agents. If successful, molecular contrast enabled OCT can improve our ability to detect early cancers, guide biopsy and cancer surgery. In addition, the molecular contrast agents can also be used for other optical imaging and spectroscopy techniques.

描述（由申请人提供）：该提案是一个多学科项目，涉及华盛顿大学生物工程、化学、病理学和医学系的研究人员。目的是开发和验证基于生物共轭金纳米笼的新型分子纳米造影剂，以提高光学相干断层扫描（OCT）在早期癌症检测中的能力。癌症的发展需要数年时间，并在转移前经历分子和结构的变化。早期癌症检测仍然是提高生存率和治疗结果的关键临床目标。 OCT是最近开发的一种非侵入性技术，可以通过体内实时组织显微解剖的横截面成像来进行“光学活检”。 OCT 提供出色的空间分辨率；然而，目前它在早期癌症检测方面取得的成功有限，主要是因为正常组织和早期癌症之间的内在光学对比度较弱且缺乏分子特异性。该提案的假设是新型分子造影剂可以增强 OCT 成像对比度和早期癌症检测的分子特异性。与其他金属纳米粒子不同，金纳米笼在近红外范围内表现出非常强的可调谐光学共振，同时保持较小的尺寸（35-65 nm）。金纳米笼可以为 OCT 成像提供强度和光谱对比度增强，并且它们可以轻松结合分子识别剂进行靶向。具体目标是：（1）利用电替代纳米化学技术开发在近红外范围内具有强吸收或散射能力的金纳米笼，并优化合成条件以扩大生产；（2）表征纳米笼的光学性质，将结果与基于离散偶极近似的理论计算结果进行比较，并量化强度和光谱OCT对比度增强；（3）进行体内动物模型研究，定量评估OCT在生物共轭纳米笼的帮助下检测早期癌症的能力； (4) 研究 OCT 使用分子造影剂检测人类食管切除标本中不典型增生和早期癌症的能力。如果成功，分子对比 OCT 可以提高我们检测早期癌症、指导活检和癌症手术的能力。此外，分子造影剂还可用于其他光学成像和光谱技术。