Infrared & X-ray Nanogold Therapy of Head & Neck Cancers

描述(申请人提供)：这项建议是基于最近的一项发现，即肿瘤可以将不吸收的小金属纳米颗粒生物转化为强红外(IR)吸收剂。在初步测试中，将无红外吸收的15 nm金纳米颗粒免疫靶向小鼠体内的人肿瘤，然后使其具有高度的红外吸收。红外吸收的放大系数可以是20倍或更多，这不能通过使用其他更大的纳米颗粒(~130 nm)来实现，这些纳米颗粒是为初始吸收IR而设计的。这一因素极大地增强了肿瘤与非肿瘤的区别。较小的体积也增强了肿瘤的摄取。IR治疗可使1 cm肿瘤迅速完全消融，而没有金剂照射的小鼠肿瘤不能得到控制。这种新的IR生物放大技术将被研究和优化，用于治疗鳞状细胞癌，鳞状细胞癌占头颈部癌症的90%。这些肿瘤过度表达表皮生长因子受体(EGFR)，共价抗EGFR抗体-金结合物将用于靶向小鼠体内的人A431肿瘤。一项显微镜研究将记录肿瘤和正常组织的反应。在第二阶段，这一新疗法将在黄金大小和靶向配体方面进行优化。红外热疗将与放射治疗相结合，因为我们最近已经证明热疗和X射线在治疗鳞癌方面具有高度的协同作用。新的联合疗法应该可以更好地避免对唾液腺和周围正常组织的损害，这是目前疗法的严重副作用之一。为了证明安全和安全限度，将进行急性、亚急性和长期毒性研究。这项工作将最终形成一种产品，供FDA批准临床试验。如果成功，这种新方法可能会改善头颈部以及其他癌症的治疗。与公共健康相关：最近开发了一种使用纳米技术的新型癌症治疗方法，在初步的动物实验中非常有希望。它还可以用于敏感的肿瘤早期检测，并实现图像引导的干预。如果成功，它可能会改善头颈部肿瘤以及其他癌症的检测和治疗。

DESCRIPTION (provided by applicant): This proposal is based on a recent discovery that tumors can bioconvert non-absorbing small metal nanoparticles into intense infrared (IR) absorbers. In preliminary tests, non-IR absorbing 15 nm gold nanoparticles were immunotargeted to human tumors in mice which then became highly IR absorbing. The amplification factor in IR absorption can be a factor of 20 or more, which is not accessible by use of other much larger nanoparticles (~130 nm) that are designed to initially absorb IR. This factor greatly enhances the tumor- to-non-tumor distinction. The small size also enhances tumor uptake. Treatment with IR led to rapid and complete tumor ablation in 1 cm tumors, whereas the tumors were not controlled in irradiated mice without the gold. This new IR bioamplification process will be studied and optimized to treat squamous cell carcinomas, which comprise 90% of head and neck cancers. Epidermal growth factor receptors (EGFr) are overexpressed by these tumors and covalent anti-EGFr antibody-gold conjugates will be used for targeting human A431 tumors in mice. A microscopic study will document tumor and normal tissue responses. In Phase II, this novel therapy will be optimized with respect to gold size and targeting ligand. The IR hyperthermia therapy will then be combined with radiotherapy, since we have recently shown that hyperthermia and x-rays are highly synergistic in treating squamous cell carcinomas. The new combination therapy should better avoid damage to salivary glands and surrounding normal tissue, which is one of the serious side effects of current therapies. In order to demonstrate safety and safety limits, an acute, subacute, and long-term toxicity study will be conducted. Work will culminate in a product for FDA approval of clinical trials. If successful, this new approach could improve the treatment of head and neck as well as other cancers. PUBLIC HEALTH RELEVANCE: A novel cancer treatment using nanotechnology has recently been developed that is very promising in preliminary animal studies. It also may be used for sensitive early detection of tumors and enable image guided interventions. If successful, it could improve detection and treatment of head and neck tumors as well as other cancers.