Gold nanoparticles as vascular disruptig agents in radiation therapy of NSCLC

 描述（由申请人提供）：抗血管生成和血管破坏疗法的最新发展显示了肿瘤血管系统作为癌症药物治疗靶点的巨大潜力。我们有一个原始的想法，使用靶向金纳米粒子（GNP）作为血管破坏剂（VDA）与临床兆伏光子束。与竞争性提案不同，我们认识到金纳米颗粒倾向于在肿瘤血管中积累，甚至可以靶向肿瘤血管，并且这些结构对于抗癌治疗可能比单独的克隆性细胞死亡更重要。由于X射线诱导的光电子行进的距离很短，即使对于临床兆伏（MV）光子照射，肿瘤的内皮细胞也将接收相当大的剂量增加。我们的初步结果包括：新的第四代纳米平台的开发、表征和测试; MV临床放射治疗射束线中剂量增强的理论和实验证据;以及优先肿瘤摄取的成像研究。该研究将确定GNP给药后放射治疗的最佳时间窗，并在临床前肺癌模型中测量治疗益处。我们的创新治疗理念与当前的临床实践高度兼容，可以在最小的患者风险下提供实质性的临床获益。

 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.