Enhancing tumor vascular damage with gold nanoparticles aided radiation therapy

描述（由申请人提供）：抗血管生成和血管破坏治疗以及大分割放射治疗的最新进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作为血管破坏剂（VDA）与临床兆伏光子束。与竞争提案不同，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。我们正在提出一种与当前临床实践高度兼容的疗法，并可提供实质性的临床获益。在成功完成目标后，我们将证明两个基本前提的有效性：1）金纳米颗粒可以有效且安全地靶向肿瘤内皮，以及2）放射治疗期间内皮细胞凋亡的发生率将与金纳米颗粒的接近度和局部浓度高度相关。

DESCRIPTION (provided by applicant): Recent developments in anti-angiogenic and vascular-disrupting therapies as well as hypofractionated radiotherapy 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 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. 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 photon irradiation. We are proposing a therapy that would be highly compatible with current clinical practice and could offer a substantial clinical benefit. Upon the successful completion of the aims, we will have demonstrated the validity of two underlying premises: 1) gold nanoparticles can be effectively, and safely, targeted to the tumor endothelium, and 2) the incidence of endothelial cell apoptosis during radiotherapy will be highly correlated to the proximity and local concentrations of gold nanoparticles.