Plasmon-Resonant Nanorods as Contrast Agents

描述(申请人提供)：利用新兴的生物医学成像方法(光学相干断层扫描或OCT)和新型造影剂(功能化金纳米棒)，将开发一种集成的、微创的方法来检测、诊断和治疗疾病状态下的细胞和组织。OCT能够在近红外(NIR)下进行细胞分辨率成像，如果有足够的对比度，就有可能在疾病的早期阶段诊断异常细胞和组织。各向异性的金纳米棒具有可调的等离子体激元响应，可以设计成在选定的近红外频率上进行强吸收或散射，从而提高OCT和相关技术的灵敏度和范围。基于孤立或聚集形式的各向异性纳米棒增强的光学对比度，将开发新的OCT方法。具有强烈和选择性近红外消光的金纳米棒将被生物分子配体功能化，以选择性地靶向生物标记物表达异常的组织。通过结合到细胞表面标记或通过细胞摄取，这些将作为定点定向的光学标记。具有磁性尖端的纳米棒可以在组织内提供额外的位置和取向控制，并促进新的动态OCT方法的发展。金属纳米棒还可以支撑极大的吸收截面，产生高度局域的热梯度，并可用于在低辐射功率下增强光诱导热疗。所提出的纳米棒增强的OCT成像系统将首先应用于组织模体，然后利用仓鼠颊囊模型通过局部加温来体内检测和治疗肿瘤细胞。OCT纳米棒技术有望作为一种集成的非侵入性系统广泛应用于需要图像引导干预的医疗问题。

DESCRIPTION (provided by applicant): An integrated, minimally invasive approach will be developed toward the detection, diagnosis, and treatment of cells and tissues in diseased states, using emerging biomedical imaging methods (optical coherence tomography, or OCT) and novel contrast agents (functionalized gold nanorods). OCT is capable of cellular-resolution imaging in the near infrared (NIR) and has the potential to diagnose abnormal cells and tissues at an early stage of disease, given sufficient contrast. Anisotropic gold nanorods exhibit tunable plasmon responses and can be engineered for strong absorption or scattering at select NIR frequencies, thereby enhancing the sensitivity and scope of OCT and related technologies. New OCT methods will be developed based on the enhanced optical contrast of anisotropic nanorods in isolated or aggregate forms. Gold nanorods with strong and selective NIR extinction will be functionalized with biomolecular ligands for selective targeting of tissues with abnormal biomarker expression. These will serve as site-directed optical labels by binding to cell-surface markers or by cell uptake. Nanorods with magnetic tips may provide additional positional and orientational control within the tissue, and enhance the development of a novel, dynamic OCT method. Metal nanorods can also support extremely large absorption cross-sections and generate highly localized thermal gradients, and can be used to enhance optically-induced hyperthermia at low radiation power. The proposed nanorod-enhanced OCT imaging system will first be applied toward tissue phantoms, then toward the in vivo detection and treatment of tumor cells by local hyperthermia using a hamster cheek pouch model. The OCT-nanorod technology is anticipated to have broad application as an integrated, noninvasive system for medical concerns which require image-guided intervention.