Enzyme-Responsive Nanoemulsions as Tumor-Specific Ultrasound Contrast Agents for

酶响应纳米乳剂作为肿瘤特异性超声造影剂

基本信息

批准号：
8138430
负责人：
Andrew P Goodwin
金额：
$ 8.93万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-07 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8138430
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 public health relevance research clinical testing response sensor success symposium tumor validation studies vaporization

项目摘要

DESCRIPTION (provided by applicant): 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 Frichet, 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. PUBLIC HEALTH RELEVANCE: This proposal describes methods to synthesize, evaluate, and employ small, non-toxic droplets that become highly visible to ultrasound only in tumor tissue, which will aid immeasurably in the early detection and imaging of breast cancer and result in improved health and prognosis of cancer patients.

描述（由申请人提供）：该提案支持Andrew Goodwin博士在癌症纳米技术中获得独立奖的应用（RFA-CA-09-015）。 Goodwin博士已经是有机合成，大分子工程和纳米技术开发的有前途的初级科学家，Goodwin博士旨在获得台式和生物学验证研究的培训，以成为癌症纳米技术方面的成功独立创新者。古德温博士于2007年在Jean Frichet教授的指导下从UC Berkeley获得了博士学位，在那里他设计了新的聚合物架构和新型释放药物机制以用于癌症治疗。然后，他继续在洪吉·戴（Hongjie Dai）教授的实验室中前往斯坦福大学CCNE，在那里他将碳纳米管和金纳米结构功能化，并带有新的合成生物相容性组件，以创建新型混合纳米结构，并具有增强的光层性特性，以实现Vivo Imaging和ex Vivo和Ex Vivo传感器。目前，他是加州大学圣地亚哥分校的癌症治疗培训计划的博士后研究员，这是NCI资助的T32计划。在过去的一年中，他一直在与Sadik Esener教授合作开发刺激反应性聚合物涂层的全氟碳微泡作为超声对比剂，仅在炎症区域激活。这项工作已经导致在几个会议上提交了专利和演讲。为了成为癌症纳米技术的生产性独立研究者，古德温博士将继续受到电气和计算机工程和纳米工程学教授的Sadik Esener教授的指导，也是UCSD癌症纳米技术卓越学（Nanotumor Center）的主任。 Esener教授是光学和声学检测技术的专家，将培训古德温博士设计仪器，以评估超声对比剂和其他检测系统。此外，Esener教授将通过指导他在研究和组成研究补助，初级科学家的指导以及实验室空间和资源的管理方面来帮助他向独立过渡。古德温博士将由摩尔斯癌症中心放射学教授，体内癌症和分子成像中心的负责人罗伯特·马特雷（Robert Mattrey）教授合作。 Mattrey教授是对全氟化合物超声对比剂的设计，制备和临床评估的专家，他将培训古德温博士在设计和实施生物学模型的设计和实施中，以评估所提出的对比剂的临床效率。这项研究将在纳米工程系的著名加利福尼亚大学圣地亚哥分校和摩尔癌中心（Moores Cancer Center）上进行，这是癌症纳米技术的有效组合。在他的独立工作中，古德温博士将适应他在UCSD开发的技术，以创建合成的纳米乳液，从而从循环中散发出来并在肿瘤部位积聚，但仅在生物标志物蛋白酶激活后才成为超声对比剂。纳米乳液将与聚合物涂层合成，该聚合物涂层可保护纳米乳液免受蒸发剂的影响，但在暴露于基质金属蛋白酶-2时会降解，这是许多癌症分泌的。该过程将暴露配体，这将导致许多纳米乳液的聚集和融合到较大的结构中，然后在成像过程中自发转化为高度活跃的超声对比剂。由于材料无毒，超声是一种廉价的成像方式，因此该提案的发展可能会导致一种强大，安全且负担得起的癌症成像和筛查方法。开发用于癌症成像和治疗的新的，有希望的纳米技术将需要从合成到电气工程再到材料科学再到生物学的许多不同研究领域的结合。在接受电气工程和动物研究方面的培训后，古德温博士将能够仅从他自己的专业知识中设计，合成，评估和验证新的纳米材料成像剂。古德温博士凭借其杰出的导师和机构支持，加上了杰出的导师和机构支持，是在独立发展创新癌症纳米技术方面表现出色的主要候选人。公共卫生相关性：该提案描述了合成，评估和采用小的无毒液滴的方法，这些液滴仅在肿瘤组织中对超声检查高度可见，这将有助于对乳腺癌的早期检测和成像，并导致改善癌症患者的健康和预后。