A Minimally Invasive Platform to Target, Image, and Treat Head and Neck Cancer

 描述（由申请人提供）： 该提案结合了荧光成像、主动靶向和随后的恶性细胞光热治疗作为治疗头颈癌的方法。近红外（NIR）激光的使用使我们能够利用金纳米棒（AuNR）的等离子体共振吸收峰（~785 nm）以及荧光染料的吸收峰（~774 nm）。我们建议用荧光染料标记抗EGFR抗体，其靶向恶性细胞上过度表达的EGFR，并将其与AuNR缀合。预计这种主动靶向将证明比先前报道的仅依赖于增强的渗透性和保留效果的方法更有效。我们的初步结果表明，近红外光热处理加热的金核受体，激发荧光，杀死约90%的肿瘤细胞在体外，并提供了40%的肿瘤体积在体内减少。据我们所知，这是第一次证明一个微创的方式结合联合收割机肿瘤靶向和荧光成像的方法，以诱导肿瘤消退的活小鼠。我们的目标是证明这个多功能平台的目标，图像和治疗肿瘤是一个改进，目前的治疗方案，为退伍军人患有头颈癌。

 DESCRIPTION (provided by applicant): This proposal combines fluorescent imaging, active targeting, and subsequent photothermal treatment of malignant cells as an approach for treating head and neck cancers. The use of a near-infrared (NIR) laser enables us to take advantage of both the plasmon resonance absorption peak of gold nanorods (AuNRs), ~785 nm, as well as the absorption peak of the fluorescent dye, ~774 nm. We propose to label anti-EGFR antibodies, which target the over-expressed EGFR on malignant cells, with a fluorescent dye and conjugate them to AuNRs. This active targeting is expected to prove more efficient than previously reported approaches that relied solely on enhanced permeability and retention effects. Our preliminary results suggest that NIR photothermal treatment heated the AuNRs, excited fluorescence, killed approximately 90% of tumor cells in vitro, and provided a 40% reduction in tumor volume in vivo. To our knowledge, this is the first demonstration of a minimally invasive modality to combine tumor targeting and fluorescent imaging with a method to induce tumor regression in live mice. We aim to demonstrate that this multifunctional platform to target, image, and treat tumors is an improvement over current treatment regimens for Veterans suffering with head and neck cancer.