CDI Type II: Cyber-Engineering Functional Nanoparticles for Targeted Drug Delivery

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。工程上的多功能药物递送工具，使多种药物同时递送是医学上的一个关键挑战。脂质体将获得显著的稳定性和功能能力，因为它有一个坚实的核心，通过强连接连接到双分子层。然而，设计和制造这种复杂的纳米粒子仍然是一个悬而未决的问题。为了实现这一目标，我们提出了一种多学科多位点策略，将传统的以实验室为中心的合成转变为基于网络的纳米设计。它的三个关键组成部分是：(1)多尺度建模层次，弥合了分子和物理细观结构之间的鸿沟；(2)利用分布式网格上的自主数据交换和学习的新颖设计和参数优化算法；(3)反馈系统，其中模拟指导改进的纳米结构的合成，而体外表征验证和改进其相应的硅表征。我们正在建立一个虚拟组织，将四个机构（加州大学戴维斯分校、科罗拉多矿业学院、卡内基梅隆大学和弗吉尼亚理工大学）联系起来，最大限度地利用我们在广泛学科领域的联合专业知识。这种网络基础设施使我们的变革方法能够以合理的计算机辅助设计功能纳米结构。所有合作伙伴将定期交换小组成员，以分享知识并获得其学科以外的培训。我们将经常举行虚拟会议和年度团队会议，最终会议包括外部合作伙伴。这项研究将开发出新型纳米颗粒作为更有效的药物递送载体。与此同时，正在开发的网络框架将作为开发连接计算科学和实验科学的实时虚拟网络的模型。例如，这项研究展示了软件如何促进新的计算基础设施，以及如何利用一个新的、多样化的团队的协同作用来跨越工程和科学中计算研究和实验研究之间的鸿沟。一个基于web的数据存储库将作为合作伙伴之间的通信中心，允许立即访问所有工具和发现。经过验证后，这些方法将通过使用同一中心向整个科学界提供。将这项研究纳入我们在当地大学教授的课程中，将告诉未来的计算科学家和实验学家，高度互动的合作如何加速发现和创新。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).Engineering versatile drug delivery vehicles that enable simultaneous delivery of several agents is a key challenge in medicine. Liposomes would gain significant stability and functional capacity from having a solid core, tethered to the bilayer by strong linkers. Nevertheless, designing and constructing such complex nanoparticles remains an open question. To achieve this goal, we present a multidisciplinary multi-site strategy that transforms conventional laboratory-centered synthesis into cyber-based nano-design. Its three key components are: (1) a multiscale modeling hierarchy bridging the divide between molecules and physical meso-structure; (2) novel design- and parameter-optimization algorithms that exploit autonomous data exchange and learning over a distributed grid; and (3) a feedback system, in which simulations guide syntheses of improved nanoconstructs, while in vitro characterizations validate and improve their corresponding in silico representations. We are establishing a virtual organization that links four institutions (UC Davis, Colorado School of Mines, Carnegie Mellon, and Virginia Tech) to maximally exploit our joint expertise across a broad spectrum of disciplines. This cyber-infrastructure enables our transformative approach to the rational computer-aided design of functional nanoconstructs. All partners will regularly exchange group members to both share knowledge and acquire training outside their disciplines. We will hold frequent virtual meetings and annual team conferences with a final conference including outside partners.This research will develop novel nanoparticles as more efficient drug delivery carriers. At the same time, the cyber framework being developing will serve as a model for developing a real-time, virtual network that links computational and experimental science. For instance, this research shows how software can facilitate new computing infrastructures and how the synergy of a fresh, diverse team can be harnessed to span the divide between computational and experimental research in engineering and science. A web-based data repository will serve as a communication hub among the partners to allow instant access to all tools and findings. After validation, these methods will be made available to the scientific community at large by using the same hub. Incorporating this research into our courses taught at our local universities will inform future computational scientists and experimentalists how a highly interactive collaboration accelerates discovery and innovation.