Enzyme-Responsive Nanoemulsions as Tumor-Specific Ultrasound Contrast Agents

6.项目摘要/摘要。 这项提案支持安德鲁·古德温博士提出的 癌症纳米技术独立奖(RFA-CA-09-015)。已经是一个有前途的大三学生了 从事有机合成、高分子工程和纳米技术开发的科学家 对于癌症成像和治疗，古德温博士寻求获得桌面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。 古德温博士在Jean教授的指导下于2007年在加州大学伯克利分校获得博士学位 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，他继续在斯坦福大学CCNE的洪杰教授的实验室 在那里，他用新的合成材料使碳纳米管和金纳米结构功能化 生物兼容组装体制造具有增强光物理性能的新型杂化纳米结构 活体成像和体外传感器的特性。目前，他是博士后研究员。 加州大学圣地亚哥分校的癌症治疗培训计划，NCI- 资助T32计划。在过去的一年里，他一直在与萨迪克·埃森纳教授合作 研制刺激响应型聚合物涂层全氟碳微泡作为超声 仅在炎症区域激活的造影剂。这项工作已经导致了 专利的申请和在几个会议上的陈述。 成为癌症纳米技术领域富有成效的独立研究员，古德温博士 将继续由Sadik Esener教授指导，Sadik Esener教授是电学和 计算机工程和纳米工程，也是加州大学圣地亚哥分校 癌症纳米技术卓越(纳米肿瘤中心)。光学和声学方面的专家 Esener教授将培训古德温博士设计检测技术的仪器 评价超声造影剂和其他检测系统。此外，埃森纳教授 将帮助古德温博士过渡到独立，指导他准备和 研究补助金的组成、初级科学家的指导和实验室的管理 空间和资源。古德温博士将由哈佛大学罗伯特·马特里教授共同指导。 摩尔癌症中心的放射学和加州大学圣迭戈分校体内癌症和 分子成像中心。马特里教授是设计、准备和临床方面的专家。 评估全氟碳超声造影剂，他将培训古德温博士 设计和实施生物模型来评估拟议的临床疗效 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，一位强有力的 结合癌症纳米技术的发展。 在他的独立工作中，古德温博士将对他在加州大学圣地亚哥分校开发的技术进行改造，以 创建合成纳米乳剂，从循环中渗出并在肿瘤处积聚 但只有在被生物标志物蛋白酶激活后才能成为超声造影剂。 纳米乳液将与聚合物涂层一起合成，以保护纳米乳液免受 蒸发，但在接触到基质金属蛋白酶-2时降解，基质金属蛋白酶-2由 很多癌症。这一过程将暴露将导致聚集和融合的配体 许多纳米乳液变成更大的结构，然后这些结构自发地转化为高度 成像过程中使用主动超声造影剂。因为这些材料是无毒和超声波的 是一种廉价的成像方式，这一提议的开发可能会导致一种强大的、 安全、经济实惠的癌症成像和筛查方法。 用于癌症成像和治疗的新的、有前途的纳米技术的开发将 需要结合许多不同的研究领域，从合成到电学 从工程学到材料科学再到生物学。在接受了电气工程和 通过动物实验，古德温博士将能够设计、合成、评估和验证新的 纳米材料显像剂完全来自他自己的专业知识。凭借他雄厚的能力和 雄心壮志加上杰出的导师和机构支持，古德温博士是一位 在创新的癌症纳米技术的自主开发方面表现出色的候选人。

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.