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

红外线的

• 批准号: 8219364
• 负责人: James F Hainfeld
• 金额: $ 39.97万
• 依托单位: NANOPROBES, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8219364
• 关键词: Ablation; Acute; Adverse effects; Animals; Anti-CEA Antibody; Antibodies; Area; Biodistribution; Cicatrix; Clinical; Clinical Chemistry; Clinical Trials; Colonic Neoplasms; Combined Modality Therapy; Data; Detection; Dose; Dose-Rate; Drug Formulations; Drug Kinetics; EGF gene; Early Diagnosis; Employee Strikes; Epidermal Growth Factor Receptor; Fever; Gold; Growth; Head and Neck Cancer; Head and Neck Neoplasms; Head and neck structure; Health; Heating; Hematology; Histopathology; Human; Injection of therapeutic agent; Lead; Left; Lethal Dose 50; Ligands; Malignant Neoplasms; Measures; Metals; Microscopic; Modality; Modeling; Mus; Nanotechnology; Nature; Normal tissue morphology; Nude Mice; Outcome; Patients; Penetration; Persons; Phase; Process; Radiation; Radiation therapy; Reporting; Roentgen Rays; Safety; Salivary Glands; Serum; Solid; Squamous cell carcinoma; Surface; Testing; Therapeutic Effect; Therapeutic heat application; Thick; Time; Tissues; Toxic effect; Tumor Tissue; Work; Xenograft procedure; absorption; base; cancer therapy; design; effective therapy; image guided intervention; improved; nanoGold; nanoparticle; nanorod; nanoshell; novel; novel strategies; overexpression; particle; research study; response; safety study; subcutaneous; theories; therapeutic target; tumor; tumor eradication; tumor growth; uptake

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.

描述（由申请人提供）：该提案是基于最近发现的，即肿瘤可以将非吸收的小金属纳米颗粒生物化成强烈的红外（IR）吸收器。在初步测试中，将吸收15 nm金纳米颗粒的非IR吸收到小鼠的人类肿瘤中被免疫靶向，然后将其高度吸收。 IR吸收中的扩增因子可以是20倍或以上，通过使用其他较大的纳米颗粒（〜130 nm），该系数无法访问，这些纳米颗粒旨在最初吸收IR。这个因素大大增强了肿瘤 - 无肿瘤的区别。小尺寸还可以增强肿瘤的摄取。 IR的治疗导致1 cm肿瘤的快速和完整的肿瘤消融，而肿瘤在没有黄金的情况下不受辐照小鼠的控制。将研究并优化这个新的IR生物放大过程，以治疗鳞状细胞癌，其中90％的头颈癌。表皮生长因子受体（EGFR）被这些肿瘤过表达，共价抗EGFR抗体 - 金偶联物将用于靶向小鼠的人A431肿瘤。一项微观研究将记录肿瘤和正常组织反应。在第二阶段，这种新颖的疗法将针对黄金大小和靶向配体进行优化。然后，IR热疗疗法将与放射疗法结合使用，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协同作用。新的组合疗法应更好地避免唾液腺和周围正常组织的损害，这是当前疗法的严重副作用之一。为了证明安全和安全限制，将进行急性，亚急性和长期毒性研究。工作将最终在FDA批准临床试验的产品中达到高潮。如果成功的话，这种新方法可以改善头部和颈部以及其他癌症的处理。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，在初步动物研究中非常有前途。它也可用于对肿瘤的敏感早期检测并实现图像引导干预措施。如果成功，它可以改善对头部和颈部肿瘤以及其他癌症的检测和治疗。