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

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。为提高光学相干断层扫描(OCT)在早期癌症检测中的能力，开发并验证了一类基于生物可调纳米金笼的新型分子纳米造影剂。癌症经过几年的发展，在转移之前会经历分子和结构的变化。早期发现癌症仍然是提高存活率和治疗结果的关键临床目标。OCT是最近发展起来的一种非侵入性技术，它可以通过活体和实时地对组织显微解剖进行横断面成像来进行光学活组织检查。OCT具有很好的空间分辨率，但目前它在早期癌症检测中的成功有限，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，并且缺乏分子特异性。该建议的假设是，新型分子造影剂可以提高OCT成像对比度和分子特异性，用于早期癌症检测。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、可调的光学共振，同时保持了较小的尺寸(35-65 nm)。金纳米笼可以同时为OCT成像提供强度和光谱对比度增强，并且它们允许分子识别试剂容易地结合以用于靶向。其具体目标是：(1)利用电流置换纳米化学开发在近红外范围内具有强吸收或散射的金纳米腔，并优化放大生产的合成条件；(2)表征纳米腔的光学性质，将结果与基于离散偶极近似的理论计算进行比较，并量化强度和OCT光谱对比增强；(3)进行体内动物模型研究，以定量评估OCT在生物共轭纳米腔辅助下检测早期癌症的能力；以及(4)利用分子造影剂研究OCT在人类食道切除标本上检测异型增生和早期癌症的能力。如果成功，启用分子对比的OCT可以提高我们发现早期癌症、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。

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.