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

描述（由申请人提供）：该提案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。在初步试验中，不吸收红外线的15纳米金纳米粒子被免疫靶向小鼠体内的人类肿瘤，然后变得高度吸收红外线。红外吸收的放大系数可以是20倍或更多，这是使用其他更大的纳米颗粒（~130纳米）所无法达到的，这些纳米颗粒最初被设计用于吸收红外。这一因素大大增强了肿瘤与非肿瘤的区别。小尺寸也增强了肿瘤的摄取。在1厘米的肿瘤中，IR治疗导致肿瘤快速和完全消融，而在没有金的照射小鼠中，肿瘤不受控制。这种新的IR生物扩增过程将被研究和优化以治疗鳞状细胞癌，鳞状细胞癌占头颈部癌症的90%。表皮生长因子受体（EGFr）在这些肿瘤中过度表达，共价抗EGFr抗体-金偶联物将用于靶向小鼠人A431肿瘤。显微镜检查将记录肿瘤和正常组织的反应。在II期，这种新疗法将在金大小和靶向配体方面进行优化。随后，红外热疗将与放射治疗相结合，因为我们最近表明，热疗和x射线在治疗鳞状细胞癌方面具有高度的协同作用。新的联合治疗应更好地避免对唾液腺和周围正常组织的损害，这是目前治疗的严重副作用之一。为了证明安全性和安全限度，将进行急性、亚急性和长期毒性研究。工作的高潮将是产品获得FDA批准的临床试验。如果成功，这种新方法可以改善头颈部和其他癌症的治疗。公共卫生相关性：最近开发了一种使用纳米技术的新型癌症治疗方法，在初步动物研究中非常有希望。它也可用于敏感的早期检测肿瘤和使图像引导干预。如果成功，它将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.