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

用于定位、成像和治疗头颈癌的微创平台

• 批准号: 10396963
• 负责人: Hadiyah-Nicole Green
• 金额: --
• 依托单位: BIRMINGHAM VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2022-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10396963
• 关键词: Adjuvant Therapy; Antibodies; Antibody Specificity; Antibody Therapy; Binding; Cell Death; Chemoresistance; Clinical; Data; Engineering; Epidermal Growth Factor Receptor; Fc Receptor; Fluorescence; Fluorescent Dyes; Gold; Head and Neck Cancer; Image; In Vitro; Intravenous; Kinetics; Knowledge; Label; Lasers; Longevity; Malignant Neoplasms; Mediating; Methods; Modality; Modeling; Mus; Palliative Care; Palpable; Patients; Performance; Permeability; Quality of life; Recurrence; Reporting; Resistance; Specificity; Techniques; Testing; Therapeutic; Time; Tissue Sample; Translating; Translations; Treatment Efficacy; Treatment Protocols; Tumor Volume; United States Department of Veterans Affairs; Veterans; Xenograft Model; absorption; antibody conjugate; base; cancer cell; cancer therapy; cell killing; cost; experience; fluorescence imaging; human model; human tissue; improved; in vivo; in vivo Model; minimally invasive; nanoparticle; nanoparticle delivery; nanorod; nanotherapy; neoplastic cell; novel; overexpression; patient population; patient prognosis; photothermal therapy; public health relevance; response; side effect; standard of care; targeted delivery; targeted imaging; targeted treatment; tumor

 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.

 描述(由申请人提供)： 这项建议结合了荧光成像、主动靶向和随后的恶性细胞光热治疗，作为治疗头颈部癌症的一种方法。近红外(NIR)激光的使用使我们能够利用金纳米棒(AuNRs)的等离子体共振吸收峰(~785 nm)和荧光染料的吸收峰~774 nm。我们建议用荧光染料标记针对恶性细胞上过度表达的EGFR的抗EGFR抗体，并将它们与AuNRs结合。这种主动靶向有望证明比以前报道的仅依赖于增强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了AuNRs，激发了荧光，在体外杀死了大约90%的肿瘤细胞，并使体内肿瘤体积减少了40%。据我们所知，这是首次展示了一种将肿瘤靶向和荧光成像与诱导活体小鼠肿瘤消退的方法相结合的微创方法。我们的目标是证明，这个多功能的靶向、成像和治疗肿瘤的平台是对患有头颈癌的退伍军人目前治疗方案的改进。