Gold nanoparticles as vascular disruptig agents in radiation therapy of NSCLC

金纳米粒子作为血管破坏剂在非小细胞肺癌放射治疗中的应用

• 批准号: 9026582
• 负责人: Ross I. Berbeco
• 金额: $ 21.63万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-03 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9026582
• 关键词: Area; Benign; Biodistribution; Blood Circulation; Blood Vessels; Cancer Model; Cell Death; Clinic; Clinical; Clinical Trials; Data; Development; Diffusion; Dose; Electrons; Endothelial Cells; Endothelium; External Beam Radiation Therapy; Funding; Generations; Goals; Gold; Health; Image; Injection of therapeutic agent; Innovative Therapy; Kidney; Kinetics; Lead; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Medicine; Molecular Target; Neoplasms in Vascular Tissue; Non-Small-Cell Lung Carcinoma; Optics; Organ; Patient risk; Patients; Penetration; Pharmaceutical Preparations; Photons; Radiation; Radiation Oncology; Radiation therapy; Research; Research Infrastructure; Rewards; Risk; Solid Neoplasm; Structure; Techniques; Testing; Therapeutic; Time; Tissues; Toxic effect; Travel; United States National Institutes of Health; base; cancer cell; cancer therapy; clinical practice; clinically significant; fluorescence imaging; image guided radiation therapy; improved; in vivo; intravenous injection; irradiation; minimal risk; mouse model; nano; nanoparticle; neovasculature; novel; pre-clinical; spectral energy; therapeutic target; translational study; tumor; tumor progression; uptake

 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.

 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。

项目成果

Key clinical beam parameters for nanoparticle-mediated radiation dose amplification.

• DOI: 10.1038/srep34040
• 发表时间: 2016-09-23
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Detappe A;Kunjachan S;Drané P;Kotb S;Myronakis M;Biancur DE;Ireland T;Wagar M;Lux F;Tillement O;Berbeco R
• 通讯作者: Berbeco R

Ultrasmall Silica-Based Bismuth Gadolinium Nanoparticles for Dual Magnetic Resonance-Computed Tomography Image Guided Radiation Therapy.

• DOI: 10.1021/acs.nanolett.6b05055
• 发表时间: 2017-03-08
• 期刊: Nano letters
• 影响因子: 10.8
• 作者: Detappe A;Thomas E;Tibbitt MW;Kunjachan S;Zavidij O;Parnandi N;Reznichenko E;Lux F;Tillement O;Berbeco R
• 通讯作者: Berbeco R