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

描述（由申请人提供）：该提议基于最近的发现，即肿瘤可以将非吸收性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，非红外吸收的15 nm金纳米颗粒免疫靶向小鼠体内的人类肿瘤，然后变得高度红外吸收。IR吸收中的放大因子可以是20或更大的因子，这是通过使用被设计为最初吸收IR的其他大得多的纳米颗粒（~130 nm）不可达到的。该因子极大地增强了肿瘤与非肿瘤的区别。小尺寸也增强了肿瘤摄取。IR治疗导致1 cm肿瘤的快速和完全的肿瘤消融，而在没有金的照射小鼠中肿瘤没有得到控制。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，其中包括90%的头颈部癌症。表皮生长因子受体（EGFr）被这些肿瘤过表达，共价抗EGFr抗体-金缀合物将用于靶向小鼠中的人A431肿瘤。显微镜研究将记录肿瘤和正常组织的反应。在第二阶段，这种新的疗法将在金的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，因为我们最近已经表明，热疗和X射线在治疗鳞状细胞癌中具有高度协同作用。新的联合治疗应更好地避免损伤唾液腺和周围正常组织，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。工作将最终在一个产品的FDA批准的临床试验。如果成功，这种新方法可以改善头颈部以及其他癌症的治疗。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。它还可以用于肿瘤的敏感早期检测，并实现图像引导干预。如果成功，它可以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.