Enzyme-Responsive Nanoemulsions as Tumor-Specific Ultrasound Contrast Agents

作为肿瘤特异性超声造影剂的酶响应纳米乳剂

• 批准号: 8536461
• 负责人: Andrew P Goodwin
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-07 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8536461
• 关键词: Acoustics; Animals; Architecture; Award; Binding; Biocompatible; Biological; Biological Markers; Biological Models; Biology; Blood Circulation; Breast Adenocarcinoma; Breast Cancer Model; CCNE1 gene; California; Cancer Center; Cancer Patient; Carbon Nanotubes; Chemicals; Chemistry; Computers; Contrast Media; Crosslinker; DNA; Detection; Development; Doctor of Philosophy; Dose; Early Diagnosis; Electrical Engineering; Emulsions; Engineering; Enzymes; Evaluation; Excision; Fluorocarbons; Funding; Gelatinase A; Goals; Gold; Head; Health; Human; Hybrids; Image; In Vitro; Inflammation; Institutional National Research Service Award; Laboratories; Legal patent; Ligands; Malignant Neoplasms; Measures; Mediating; Mentors; Mentorship; Methods; Microbubbles; Modeling; Mus; Nanostructures; Nanotechnology; Optics; Organic Synthesis; Pathway interactions; Peptide Hydrolases; Peptides; Phase; Polymers; Postdoctoral Fellow; Preparation; Process; Property; Radiology Specialty; Rebecca and John Moores UCSD Cancer Center; Research; Research Personnel; Research Project Grants; Research Proposals; Resources; Science; Scientist; Screening procedure; Site; Stimulus; Structure; Surface; Suspension substance; Suspensions; System; Techniques; Technology; Testing; Therapeutic; Thrombin; Thrombosis; Training; Training Programs; Tumor Tissue; Ultrasonography; Universities; Work; base; cancer imaging; cancer therapy; clinical efficacy; crosslink; design; drug mechanism; imaging modality; improved; in vivo; innovation; instrumentation; malignant breast neoplasm; molecular imaging; nanoemulsion; nanoengineering; nanomaterials; nanoscale; novel; outcome forecast; overexpression; perfluoropentane; professor; research clinical testing; response; sensor; success; symposium; tumor; validation studies; vaporization

6. PROJECT SUMMARY/ABSTRACT. This proposal supports the application of Dr. Andrew Goodwin for a Pathway to Independence Award in Cancer Nanotechnology (RFA-CA-09-015). Already a promising junior scientist in organic synthesis, macromolecular engineering, and nanotechnology development for cancer imaging and therapy, Dr. Goodwin seeks to obtain training in benchtop and biological validation studies to become a successful independent innovator in cancer nanotechnology. Dr. Goodwin obtained his Ph. D from UC Berkeley in 2007 under the direction of Prof. Jean Fr¿chet, where he designed new polymer architectures and novel release drug mechanisms for cancer therapy. He then continued to the Stanford University CCNE in the labs of Prof. Hongjie Dai, where he functionalized carbon nanotubes and gold nanostructures with new synthetic biocompatible assemblies to create novel hybrid nanostructures with enhanced photophysical properties for in vivo imaging and ex vivo sensors. Currently, he is a Postdoctoral Fellow in the Cancer Therapeutics Training Program at the University of California, San Diego, an NCI- funded T32 program. For the past year, he has been working with Prof. Sadik Esener on developing stimulus-responsive polymer-coated perfluorocarbon microbubbles as ultrasound contrast agents that activate only in regions of inflammation. Already this work has resulted in the filing of a patent and presentation at several conferences. To become a productive independent investigator in cancer nanotechnology, Dr. Goodwin will continue to be mentored by Prof. Sadik Esener, who is a Professor of Electrical and Computer Engineering and Nanoengineering and also the Director of the UCSD Center for Cancer Nanotechnology Excellence (Nanotumor Center). An expert in optical and acoustic detection technologies, Prof. Esener will train Dr. Goodwin in designing instrumentation for evaluation of ultrasound contrast agents and other detection systems. In addition, Prof. Esener will aid Dr. Goodwin in his transition to independence by mentoring him in the preparation and composition of research grants, mentorship of junior scientists, and management of laboratory space and resources. Dr. Goodwin will be co-mentored by Prof. Robert Mattrey, Prof. of Radiology at the Moores Cancer Center and the head of the UCSD In vivo Cancer and Molecular Imaging Center. Prof. Mattrey is an expert in the design, preparation, and clinical evaluation of perfluorocarbon ultrasound contrast agents, and he will train Dr. Goodwin in the design and implementation of biological models to evaluate the clinical efficacy of the proposed contrast agents. This research will be performed at the renowned University of California, San Diego in the Department of Nanoengineering and the Moores Cancer Center, a potent combination for the development of cancer nanotechnology. In his independent work, Dr. Goodwin will adapt the technology he developed at UCSD to create synthetic nanoemulsions that extravasate from circulation and accumulate at the tumor site but only become ultrasound contrast agents after activation by biomarker proteases. Nanoemulsions will be synthesized with a polymer coating that protects the nanoemulsion from vaporization but degrades when exposed to matrix metalloproteinase-2, which is secreted by many cancers. This process will expose ligands that will cause the aggregation and fusion of many nanoemulsions into larger structures, which then spontaneously transform into highly active ultrasound contrast agents during imaging. As the materials are non-toxic and ultrasound is an inexpensive imaging modality, development of this proposal could result in a powerful, safe, and affordable method of cancer imaging and screening. The development of new, promising nanotechnologies for cancer imaging and therapy will require the combination of many different fields of research, from synthesis to electrical engineering to materials science to biology. After receiving training in electrical engineering and animal studies, Dr. Goodwin will be able to design, synthesize, evaluate, and validate new nanomaterial imaging agents solely from his own expertise. With his substantial ability and ambition combined with outstanding mentors and institutional support, Dr. Goodwin is a prime candidate to excel in the independent development of innovative cancer nanotechnologies.

6.项目总结/摘要。 该提案支持安德鲁·古德温博士申请一个途径， 癌症纳米技术独立奖（RFA-CA-09-015）。已经是个有前途的后辈了 有机合成、高分子工程和纳米技术开发科学家 对于癌症成像和治疗，古德温博士寻求获得台式和生物学方面的培训， 验证研究，成为癌症纳米技术的成功独立创新者。 古德温博士于2007年在吉恩教授的指导下获得加州大学伯克利分校的博士学位 在那里，他设计了新的聚合物结构和新的药物释放机制， 癌症治疗然后他继续到斯坦福大学CCNE在洪杰教授的实验室 戴，在那里他官能化碳纳米管和金纳米结构与新的合成 生物相容性组件以产生具有增强的生物物理特性的新型混合纳米结构 体内成像和离体传感器的特性。目前，他是英国皇家科学院的博士后研究员 加州大学圣地亚哥分校的癌症治疗培训项目，一个NCI- T32计划在过去的一年里，他一直与Sadik Esener教授合作， 开发刺激响应聚合物涂层的氟碳微泡作为超声 仅在炎症区域激活的造影剂。这项工作已经导致 申请专利并在多个会议上发表演讲。 为了成为癌症纳米技术的独立研究者，古德温博士 将继续由Sadik Esener教授指导，他是电气和电子工程学教授， 计算机工程和纳米工程，也是加州大学圣地亚哥分校中心主任， 癌症纳米技术卓越（纳米肿瘤中心）。光学和声学专家 检测技术，Esener教授将培训古德温博士设计仪器， 超声造影剂和其他检测系统的评价。此外，Esener教授 将帮助古德温博士过渡到独立，指导他准备和 研究赠款的组成、青年科学家的导师制和实验室的管理 空间和资源。Goodwin博士将由Robert Mattrey教授共同指导， Moores癌症中心的放射学和UCSD体内癌症的负责人， 分子影像中心。Mattrey教授是设计、制备和临床方面的专家， 评估全氟化碳超声造影剂，他将培训古德温博士在 设计和实施的生物模型，以评估临床疗效的建议， 造影剂。这项研究将在著名的加州大学旧金山分校进行 迭戈在纳米工程系和摩尔癌症中心，一个强大的 癌症纳米技术的发展。 在他的独立工作中，古德温博士将把他在加州大学圣地亚哥分校开发的技术， 产生从循环中渗出并在肿瘤处积聚的合成纳米乳剂 但仅在被生物标志物蛋白酶激活后成为超声造影剂。 纳米乳液将与聚合物涂层一起合成，该聚合物涂层保护纳米乳液免受 蒸发，但当暴露于基质金属蛋白酶-2时降解，基质金属蛋白酶-2是由 许多癌症。这个过程将暴露配体，这将导致聚集和融合 许多纳米乳液转化为更大的结构，然后自发地转化为高度分散的纳米乳液。 在成像期间激活超声造影剂。由于材料无毒， 是一种廉价的成像方式，该提案的发展可能会导致一个强大的， 安全，负担得起的癌症成像和筛查方法。 新的、有前途的用于癌症成像和治疗的纳米技术的发展将 需要结合许多不同的研究领域，从合成到电子 从工程到材料科学再到生物学。在接受电气工程和 动物研究，古德温博士将能够设计，合成，评估和验证新的 纳米材料成像剂完全来自他自己的专业知识。以他的能力和 抱负与杰出的导师和机构的支持相结合，古德温博士是一个总理 候选人擅长独立开发创新的癌症纳米技术。