Enhancing tumor vascular damage with gold nanoparticles aided radiation therapy

金纳米粒子辅助放射治疗增强肿瘤血管损伤

• 批准号: 8507641
• 负责人: Ross I. Berbeco
• 金额: $ 7.98万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-09 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8507641
• 关键词: Address; Adjuvant; Apoptosis; Biodistribution; Blood Vessels; Cell Death; Cell membrane; Clinic; Clinical; Clinical Trials; Collaborations; Computer Simulation; Computer Vision Systems; Development; Diffusion; Disease; Dose; Electrons; Endothelial Cells; Endothelium; Future; Goals; Gold; Human; Image; In Situ Nick-End Labeling; In Vitro; Incidence; Injection of therapeutic agent; Integrins; Kinetics; Lead; Linear Accelerator Radiotherapy Systems; Location; Malignant Neoplasms; Malignant neoplasm of pancreas; Measures; Medicine; Microscopy; Mus; Neoplasm Metastasis; Neoplasms in Vascular Tissue; New England; Normal tissue morphology; Oncology Group; Organ; Patients; Photons; Procedures; Production; Radiation; Radiation Oncology; Radiation therapy; Reporting; Source; Speed; Structure; Surface; Techniques; Testing; Therapeutic; Time; Tissues; Toxic effect; Travel; Universities; bioaccumulation; cancer cell; cancer therapy; cell killing; clinical practice; in vivo; irradiation; mouse model; nanomedicine; nanoparticle; neovascular; neovasculature; novel strategies; pancreatic neoplasm; programs; therapeutic target; tumor; tumor eradication; uptake

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.

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。

项目成果

Nanoparticle Mediated Tumor Vascular Disruption: A Novel Strategy in Radiation Therapy.

• DOI: 10.1021/acs.nanolett.5b03073
• 发表时间: 2015-11-11
• 期刊: Nano letters
• 影响因子: 10.8
• 作者: Kunjachan S;Detappe A;Kumar R;Ireland T;Cameron L;Biancur DE;Motto-Ros V;Sancey L;Sridhar S;Makrigiorgos GM;Berbeco RI
• 通讯作者: Berbeco RI

Targeted radiotherapy with gold nanoparticles: current status and future perspectives.

• DOI: 10.2217/nnm.14.55
• 发表时间: 2014-05
• 期刊: Nanomedicine (London, England)
• 作者: Ngwa W;Kumar R;Sridhar S;Korideck H;Zygmanski P;Cormack RA;Berbeco R;Makrigiorgos GM
• 通讯作者: Makrigiorgos GM