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治疗的最新进展表明，肿瘤血管作为癌症医学的治疗靶点具有巨大的潜力。我们有一个独到的想法，将靶向金纳米颗粒(GNP)作为血管干扰剂(VDA)与临床上的巨伏光子束结合使用。与竞争方案不同，我们认识到，金纳米颗粒往往会在肿瘤血管中积聚，甚至可以被靶向肿瘤血管，而且这些结构对于抗癌治疗可能比克隆细胞死亡本身更重要。由于X射线诱导的光电子传播的距离很短，即使是临床上的兆伏(MV)光子照射，肿瘤内皮细胞也将获得相当大的剂量增加。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临床放射治疗光束线剂量增强的理论和实验证据；以及肿瘤优先摄取的成像研究。这项拟议的研究将确定GNP给药后放射治疗的最佳时间窗口，并在临床前肺癌模型中衡量治疗益处。我们的创新治疗理念与当前的临床实践高度兼容，可以在最大限度降低患者风险的情况下提供实质性的临床益处。

 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.