Hybrid Nanoparticles in Imaging and Therapy of Prostate*

混合纳米颗粒在前列腺成像和治疗中的应用*

• 批准号: 7127272
• 负责人: Kattesh V Katti
• 金额: $ 60.53万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-29 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7127272
• 关键词: SCID mouse; bioimaging /biomedical imaging; bombesin; chemical synthesis; computed axial tomography; computer simulation; computer system design /evaluation; contrast media; gold; image enhancement; molecular /cellular imaging; nanotechnology; neoplasm /cancer radiation therapy; neoplasm /cancer radiodiagnosis; particle; phantom model; pharmacokinetics; prostate neoplasms; swine; technology /technique development; xenotransplantation

DESCRIPTION (provided by applicant): The University of Missouri (MU) Cancer Nanotechnology Platform (CNP) is the culmination of long-standing interdisciplinary partnerships in departments within the School of Medicine, the College of Arts and Science, the College of Veterinary Medicine, the Ellis Fischel Cancer Center, the Missouri University Research Reactor and the College of Engineering. Our CNP's overarching goal focuses on developing hybrid gold nanoparticle-based molecular imaging agents and targeted therapeutic agents that are effective in the diagnosis and treatment of prostate cancer. The specific objectives of our CNP include the following: (i) Synthesize and use a library of gold nanoparticles (AuNPs) for conjugation with prostate tumor-specific bombesin peptides. Investigate the photophysical properties, dispersity, and size-dimension measurements on these gold nanoparticles. (ii) Investigate biolocalization, pharmacokinetics and in vivo profiles of AuNPs stabilized with starch, agarose, and arabinagalactan protein (gum Arabic) in pigs. We will optimize analytical protocols, using techniques of neutron activation analysis (NAA), atomic absorption and radiochemical analysis using Au-198 nanoparticulate tracer, for the accurate estimation of AuNPs/gold metal in tissues and biological fluids, (iii) Develop new theoretical models, computations and simulations for the interaction of AuNPs with cells, (iv) Investigate the utility of AuNPs and bombesin-conjugated hybrid AuNPs as image enhancers in computed tomographic (CT) and ultrasound (US) imaging of prostate tumors in SCID mice implanted with human prostate cancer xenografts and with experimental modeling, simulations and studies on anthropomorphic phantom models of prostate cancer, (v) Optimize production of nanoparticulate a-emitting Au-198/199 and their utility for designing and developing tumor-specific Au-198/199-nanoparticlelabeled bombesin peptides for prostate tumor therapy. These studies will validate that multiple atoms of fiemitting Au-198 isotope, characteristic of nanoparticulate gold, will deliver significantly higher therapeutic payload to tumor sites than any conventional therapy. The MU Nanoparticles Production Core Facility will serve as a research and production resource for the unhindered supply of AuNPs to all investigators within the CNP program. The CNP provides unique opportunities for professionals from diverse academic backgrounds to be involved in collaborative scientific interactions that further our interdisciplinary research, education and product development program. We will apply principles of nanoscience and nanotechnology to develop innovative molecular imaging and therapeutic approaches to combat prostate cancer.

描述（由申请人提供）： 密苏里大学 (MU) 癌症纳米技术平台 (CNP) 是医学院、艺术与科学学院、兽医学院、埃利斯菲舍尔癌症中心、密苏里大学研究堆和工程学院。我们 CNP 的总体目标侧重于开发基于混合金纳米颗粒的分子成像剂和可有效诊断和治疗前列腺癌的靶向治疗剂。我们的 CNP 的具体目标包括以下内容：(i) 合成并使用金纳米颗粒 (AuNP) 库与前列腺肿瘤特异性铃蟾肽结合。研究这些金纳米粒子的光物理性质、分散性和尺寸测量。 (ii) 研究用淀粉、琼脂糖和阿拉伯半乳聚糖蛋白（阿拉伯树胶）稳定的 AuNP 在猪体内的生物定位、药代动力学和体内特征。我们将利用中子活化分析（NAA）、原子吸收和使用 Au-198 纳米颗粒示踪剂的放射化学分析技术来优化分析方案，以准确估计组织和生物体液中的 AuNPs/金金属，（iii）开发新的理论模型、AuNPs 与细胞相互作用的计算和模拟，(iv) 研究 AuNPs 和铃蟾肽共轭杂化 AuNPs 作为计算机断层扫描 (CT) 中图像增强剂的效用对植入人类前列腺癌异种移植物的 SCID 小鼠中的前列腺肿瘤进行超声（美国）成像，并对前列腺癌拟人化模型进行实验建模、模拟和研究，(v) 优化纳米粒子发射 Au-198/199 的生产和它们可用于设计和开发用于前列腺肿瘤治疗的肿瘤特异性 Au-198/199 纳米颗粒标记的铃蟾肽肽。这些研究将验证发射 Au-198 同位素的多个原子（纳米颗粒金的特征）将比任何传统疗法为肿瘤部位提供显着更高的治疗有效负载。 MU 纳米颗粒生产核心设施将作为研究和生产资源，为 CNP 项目内的所有研究人员不受阻碍地供应 AuNP。 CNP 为来自不同学术背景的专业人士提供了参与科学协作互动的独特机会，从而进一步推进我们的跨学科研究、教育和产品开发计划。我们将应用纳米科学和纳米技术的原理来开发创新的分子成像和治疗方法来对抗前列腺癌。