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.



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