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.