Gold nanoparticles as vascular disruptig agents in radiation therapy of NSCLC

金纳米粒子作为血管破坏剂在非小细胞肺癌放射治疗中的应用

基本信息

批准号：
8893262
负责人：
Ross I. Berbeco
金额：
$ 18.02万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-03-03 至 2017-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8893262
关键词：
Area Benign Biodistribution Blood Circulation Blood Vessels Cancer Model Cell Death Clinic Clinical Clinical Trials Data Development Diffusion Dose Electrons Endothelial Cells Endothelium External Beam Radiation Therapy Funding Generations Goals Gold Image Injection of therapeutic agent Innovative Therapy Kidney Kinetics Lead Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of lung Measures Medicine Molecular Target Neoplasms in Vascular Tissue Non-Small-Cell Lung Carcinoma Optics Organ Patient risk Patients Penetration Pharmaceutical Preparations Photons Radiation Radiation Oncology Radiation therapy Research Research Infrastructure Rewards Risk Solid Neoplasm Structure Techniques Testing Therapeutic Time Tissues Toxic effect Travel United States National Institutes of Health base cancer cell cancer therapy clinical practice clinically significant fluorescence imaging image guided radiation therapy improved in vivo intravenous injection irradiation minimal risk mouse model nano nanoparticle neovasculature novel pre-clinical public health relevance spectral energy therapeutic target translational study tumor tumor progression uptake

项目摘要

DESCRIPTION (provided by applicant): Recent developments in anti-angiogenic and vascular-disrupting therapies have shown the great potential of tumor vasculature as a therapeutic target for cancer medicine. We have an original idea for using targeted gold nanoparticles (GNP) as vascular disruptive agents (VDA) in conjunction with clinical megavoltage photon beams. Unlike competing proposals, we recognize that gold nanoparticles tend to accumulate in, and can even be targeted for, tumor blood vessels and that these structures may be more important for anti-cancer therapy than clonogenic cell death alone. Due to the short distance traveled by x-ray induced photoelectrons, the endothelial cells of the tumor will receive a sizable boost in dose, even for clinical megavoltage (MV) photon irradiation. Our preliminary results include: development, characterization and testing of a novel 4th generation nano-platform; theoretical and experimental evidence of dose enhancement in a MV clinical radiation therapy beam-line; and imaging studies of preferential tumor uptake. The proposed study will determine the optimal time window for radiation therapy after GNP administration and measure the therapy benefit in a preclinical lung cancer model. Our innovative therapy concept is highly compatible with current clinical practice and could offer a substantial clinical benefit with minimal patient risk.

描述（由申请人提供）：抗血管生成和血管破坏疗法的最新进展表明肿瘤脉管系统作为癌症医学治疗靶点的巨大潜力我们有一个使用靶向金纳米粒子（GNP）作为血管破坏药物的原创想法。与临床兆伏光子束相结合的药物（VDA）与竞争性提案不同，我们认识到金纳米颗粒倾向于积聚在肿瘤血管中，甚至可以靶向肿瘤血管，并且这些结构可能是肿瘤血管中的靶点。对于抗癌治疗比单独的克隆性细胞死亡更重要，由于 X 射线诱导光电子传播的距离较短，即使对于临床兆伏 (MV) 光子照射，肿瘤的内皮细胞也会受到相当大的剂量增加。我们的初步成果包括：新型第四代纳米平台的开发、表征和测试；MV 临床放射治疗束线剂量增强的理论和实验证据以及优先肿瘤的成像研究；拟议的研究将确定 GNP 给药后放射治疗的最佳时间窗口，并测量临床前肺癌模型中的治疗效果，我们的创新治疗理念与当前的临床实践高度兼容，并且可以为最少的患者提供实质性的临床益处。风险。