Targeted Gold Nanoparticle-Bioconjugates for Imaging Breast Cancer

用于乳腺癌成像的靶向金纳米颗粒生物共轭物

• 批准号: 7278911
• 负责人: Raghuraman Kannan
• 金额: $ 14.95万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-20 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7278911
• 关键词: Adipose tissue; Affinity; Animal Model; Benign; Binding; Biology; Bombesin; Bombesin Receptor; Breast; Breast Cancer Cell; Breast Cancer Detection; Breast Cancer Early Detection; Breast Microcalcification; Caliber; California; Cancer Patient; Cancerous; Case Study; Cells; Clinical Trials; Computers; Condition; Contrast Media; Cutaneous; Death Rate; Detection; Development; Devices; Diagnosis; Diagnostic; Dose; Ductal; Early Diagnosis; Effectiveness; Enhancers; Evaluation; Exhibits; Funding; Gel; Generations; Goals; Gold; Human; Image; Image Enhancement; Implant; In Situ; In Vitro; Invasive; Investigation; Lead; Lesion; Libraries; Malignant - descriptor; Malignant Neoplasms; Mammary Gland Parenchyma; Mammary Neoplasms; Mammography; Measurement; Mediating; Medicine; Methods; Modality; Nanotechnology; Noise; Outcome; Patients; Peptides; Phase; Physical Examination; Population; Property; Protocols documentation; Radiation; Rate; Research; Resolution; Roentgen Rays; SCID Mice; Screening for cancer; Screening procedure; Self-Examination; Sepharose; Shapes; Site; Specificity; Staging; Survival Rate; Time; Tissues; Tomography, Computed, Scanners; Transmission Electron Microscopy; Tumor Specific Peptide; Universities; Woman; Work; X-Ray Computed Tomography; Xenograft procedure; analog; attenuation; base; breast cancer diagnosis; design; imaging probe; improved; in vivo; innovation; instrument; malignant breast neoplasm; molecular imaging; nanoparticle; nanoparticulate; nanoprobe; nanoscience; nanosized; particle; phantom model; retinal rods; simulation; size; tomography; tumor; tumor xenograft

DESCRIPTION (provided by applicant): This application describes the design of new gold nanoparticle based bioconjugates derived from synthetic bombesin (BBN) analogues to produce a new generation of site-directed computed tomography (CT) imaging agents for specific in vivo targeting of breast cancer cells. With the overarching goal of visualizing smaller lesion (and therefore earlier cancer detection) with better specificity, this work has the potential to increase the survival rate from breast cancer. Specifically, this application will explore whether targeted gold nanoparticles are capable of producing contrast enhancement (increased x-ray attenuation) so that CT can be used in precise and accurate functional/molecular imaging of breast cancer. Our specific aims for the proposed project are to: (i) Optimize synthetic protocols for targeted gold nanoparticles (AuNPs) conjugated to tumor specific peptide; (ii) Determine the concentrations of gold nanoparticles necessary to induce image contrast in CT imaging using anthropomorphic phantom models of the human breast, including malignant lesions; and (iii) Investigate the utility of Bombesin conjugated AuNPs as image enhancers in computer tomographic (CT) imaging of breast tumors in SCID mice implanted with human breast cancer xenografts. Phantom studies will be performed to evaluate the concentration of AuNP required to produce sufficient contrast to effectively detect breast cancer for a specifically designed Breast CT scanner. This assessment will be done with respect to radiation dose and the size of the lesion; it is anticipated that improved contrast will lead to earlier detection of minimal breast cancer (in situ and minimally invasive). Approaches and methods to conjugate different sizes and shapes of gold nanoparticles (AuNPs) with synthetic BBN analogues that maintain or enhance high breast cancer cell binding with good in vitro and in vivo stability, will be developed. The most promising targeted AuNP-BBN candidates will be evaluated in SCID mice implanted with breast tumor xenografts, to assess their ability to target breast tumors. The goal of these studies is to provide targeted AuNP-BBN analogues that could be developed, via human clinical trials, into effective molecular imaging agents for early diagnostic application in breast tumor patients. The specific objective of our application encompassing the development of new molecular imaging probes, for the early detection of breast cancer, using nanotechnology principles is directly relevant to the overall outcomes sought within the current RFA "PAR-06-475- Nanoscience and nanotechnology in Biology and Medicine (R21)". The proposed work will develop an enhancement of current Computer Tomography (CT) imaging of the breast. The research will utilize nanosized gold particles that are approximately 1000 times smaller than a human cell to generate X-ray contrast that would be detected by a CT-imaging instrument external to the body. If molecules specific to breast cancer are attached to the gold nanoparticles so that they locate in the cells of breast cancer, the contrast generated would allow the cancer to be more readily detected. This has the potential to improve the early detection and diagnosis of breast cancer.

描述（由申请人提供）：本申请描述了基于合成铃蟾肽（BBN）类似物的新型金纳米颗粒生物缀合物的设计，以生产新一代定点计算机断层扫描（CT）成像剂，用于体内特异性靶向乳腺癌细胞。这项工作的总体目标是以更好的特异性可视化更小的病变（从而更早地检测癌症），因此有可能提高乳腺癌的生存率。具体来说，该应用将探索靶向金纳米粒子是否能够产生对比度增强（增加X射线衰减），以便CT可以用于乳腺癌的精确和准确的功能/分子成像。我们拟议项目的具体目标是：（i）优化与肿瘤特异性肽缀合的靶向金纳米颗粒（AuNP）的合成方案； (ii) 使用人类乳腺（包括恶性病变）的拟人体模模型，确定在 CT 成像中引起图像对比度所需的金纳米颗粒浓度； (iii) 研究 Bombesin 缀合的 AuNP 作为图像增强剂在植入人乳腺癌异种移植物的 SCID 小鼠乳腺肿瘤的计算机断层 (CT) 成像中的效用。将进行模型研究，以评估为专门设计的乳房 CT 扫描仪产生足够的对比度以有效检测乳腺癌所需的 AuNP 浓度。该评估将根据辐射剂量和病变大小进行；预计对比度的提高将有助于更早地发现微小乳腺癌（原位和微创）。将开发将不同尺寸和形状的金纳米颗粒 (AuNP) 与合成 BBN 类似物缀合的方法和方法，以维持或增强乳腺癌细胞的高结合力，并具有良好的体外和体内稳定性。最有前途的靶向 AuNP-BBN 候选药物将在植入乳腺肿瘤异种移植物的 SCID 小鼠中进行评估，以评估其靶向乳腺肿瘤的能力。这些研究的目标是提供靶向 AuNP-BBN 类似物，通过人体临床试验将其开发成有效的分子成像剂，用于乳腺肿瘤患者的早期诊断应用。我们应用的具体目标包括开发新的分子成像探针，利用纳米技术原理早期检测乳腺癌，与当前 RFA“PAR-06-475-生物学和医学中的纳米科学和纳米技术 (R21)”中寻求的总体结果直接相关。拟议的工作将开发现有乳房计算机断层扫描 (CT) 成像的增强功能。该研究将利用比人体细胞小约 1000 倍的纳米金颗粒来产生 X 射线对比，并由体外 CT 成像仪器检测到。如果乳腺癌特异性分子附着在金纳米颗粒上，从而定位在乳腺癌细胞中，产生的对比度将使癌症更容易被检测到。这有可能改善乳腺癌的早期检测和诊断。