An Informatics Resource for Targeted Nanoparticle Therapeutics

项目IV -大卫9月，博士 标题：靶向纳米粒子治疗的信息学资源 每年，数十亿美元被用于开发和测试用于治疗的新药 癌症。尽管这些化合物在预试验体外筛选中表现良好，但它们在体内的失败通常是由于它们在体外筛选中表现不佳而引起的。 由于错误分布、交叉反应性或非特异性引起的毒性问题， 在其他地方积累。使用纳米颗粒的高亲和力药物的靶向递送有望减轻 许多这些困难;然而，仍然有许多未知数方面的物理和 这些纳米级治疗剂的药理学性质。该项目的重点是开发一个 纳米粒子信息学资源，将包括一个全面的分类数据库， 纳米颗粒的药代动力学和药效学建模技术和工具箱。这 资源将由三名计算生物学家（Baker，Pappu和Sept）组成的团队开发。它将 整理与这些纳米颗粒的药理学行为相关的信息，包括摄取， 这些颗粒的降解和清除，以及结合每个颗粒的能力， 配体和小分子。此外，该资源将开发和应用药代动力学和 药效学模型来模拟靶向纳米颗粒作为药物递送剂的工作。通过 为这些信息提供全面和集中的资源，该资源将允许 来自纳米科学或制药方面的研究人员寻找兼容的技术， 这些解决方案将使其产品能够用于治疗、诊断或预防癌症。在这 以这种方式，该项目将直接促进纳米颗粒技术的发展，特别是那些在 本SCCNE提案中的项目I-III。

Project IV - David Sept, Ph.D. Title: An Informatics Resource for Targeted Nanoparticle Therapeutics Each year, many billions of dollars are spent on the development and testing of new drugs for the treatment of cancer. Although these compounds perform well in pre-trial in vitro screens, their failure in vivo is typically attributed to problems with toxicity originating from misdistribution, cross-reactivity, or non-specific accumulation at other sites. Targeted delivery of high affinity drugs using nanoparticles promises to alleviate many of these difficulties; however, there are still many unknowns with respect to the physical and pharmacological properties of such nanoscale therapeutics. The focus of this project is to develop a nanoparticle informatics resource that will include a comprehensive taxonomical database of available technologies and a toolbox for pharmacokinetics and pharmacodynamics modeling of nanoparticles. This resource will be developed by a team of three computational biologists (Baker, Pappu, and Sept). It will collate information relevant to the pharmacological behavior of these nanoparticles, including the uptake, degradation and clearance of these particles, as well as the ability to conjugate each particle with binding ligands and small molecules. Additionally, the resource will develop and apply both pharmacokinetics and pharmacodynamics models to simulate the workings of targeted nanoparticles as drug delivery agents. By providing a comprehensive and centralized resource for such information, this resource will allow researchers from either the nanoscience or pharmaceutical side to find compatible technologies and solutions that will enable their product to be used in the treatment, diagnosis or prevention of cancer. In this manner, this project will directly facilitate the development of nanoparticle technologies; particularly those in Projects I - III within this SCCNE proposal.