Enhancing tumor vascular damage with gold nanoparticles aided radiation therapy

描述(申请人提供)：抗血管生成和血管破坏治疗以及低分割放射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，将靶向的金纳米颗粒作为血管干扰剂(VDA)与临床上的兆伏光子束结合使用。与竞争方案不同，我们认识到金纳米颗粒倾向于在肿瘤血管中积聚，甚至可以针对肿瘤血管，并且这些结构对于抗癌治疗可能比克隆形成细胞死亡更重要。由于X射线诱导的光电子传播的距离很短，即使在临床上进行兆伏光子照射，肿瘤内皮细胞也将获得相当大的剂量增加。我们正在提出一种疗法，它将与当前的临床实践高度兼容，并可能提供实质性的临床益处。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和安全地靶向肿瘤内皮细胞，2)放射治疗过程中内皮细胞凋亡的发生率将与金纳米颗粒的接近程度和局部浓度高度相关。 公共卫生相关性：该项目的目标是在放射治疗过程中通过使用金纳米颗粒来改进癌症治疗，这种纳米颗粒专门针对肿瘤血管。在治疗性照射期间，这些纳米粒子将向其周围发出额外的辐射剂量。随之而来的肿瘤血管的崩溃可能会导致癌细胞大规模死亡，并有可能阻止转移。

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. PUBLIC HEALTH RELEVANCE: The goal of this project is the improvement of cancer therapy by employing gold nanoparticles, specifically targeted to tumor blood vessels, during radiation therapy. These nanoparticles will give off an extra radiation dose to their immediate surroundings during therapeutic irradiation. The ensuing collapse of the tumor vasculature could lead to large scale cancer cell death and potentially halt metastasis.