DENDRIMER ARCHITECTURAL MODELING FOR THE NEW CANCER THERAPEUTIC APPLICATIONS

新癌症治疗应用的树枝状大分子结构建模

• 批准号: 8364235
• 负责人: INHAN LEE
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364235
• 关键词: Algorithms; Architecture; Biomedical Research; Cells; Chemicals; Complex; Dendrimers; Devices; Funding; Gene Delivery; Gene Targeting; Genes; Grant; High Performance Computing; Image; Malignant Neoplasms; Mental Depression; Michigan; Modeling; Nanotechnology; National Center for Research Resources; Oligonucleotides; Organ; Polymers; Principal Investigator; RNA Interference; Research; Research Infrastructure; Resources; Source; Specificity; Structure; System; Therapeutic; Thermodynamics; United States National Institutes of Health; Universities; Work; abstracting; base; cancer therapy; computer studies; cost; molecular dynamics; novel therapeutics; simulation; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Molecular Dynamics Simulation, dendrimer, cancer therapeutics, RNA interference Abstract: The University of Michigan Center for Biologic Nanotechnology (UMCBN) is developing new therapeutics for cancer based on dendritic polymer architecture. Current plan is to assemble functional dendrimers in a defined way to make a dendrimer cluster with multiple functionality. One unit can be a dendrimer with targeting moiety, a second unit a dendrimer with sensing, a third with imaging the tumor and a fourth with carrying and delivering the actual therapeutic. Then all units (shell) are attached to another dendrimer (core). In this manner, dendritic polymers can form complex structures that achieve all of the necessary therapeutic aspects against a cancer. Structural studies using MD simulations are crucial in achieving a multi-functional device from a dendrimer complex. We will predict the optimal parameters for a device and reduce considerable chemical bench work through these computational studies. In addition to cancer therapy, dendrimers have been proved to be used as excellent gene delivery vehicles. We will use dendrimer as a potential RNA interference delivery system. Once the efficacy is proved, this new type of RNA interference can be occurred as cell or organ specific manner. We will perform MD simulations among oligonucleotides and dendrimers to find optimal conditions for this task. Sequence specificities and thermodynamic parameters of oligonucleotides targeting certain genes will also be calculated using our own algorithms. Target genes will be depression related genes in addition to cancer related ones.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 分子动力学模拟，树枝状大分子，癌症治疗，RNA干扰 摘要：密歇根大学生物纳米技术中心(UMCBN)正在开发基于树枝状聚合物结构的癌症新疗法。目前的计划是以特定的方式组装功能树枝状大分子，以形成具有多种功能的树枝状大分子簇。一个单元可以是具有靶向部分的树状分子，第二个单元可以是具有传感功能的树状分子，第三个单元可以是肿瘤成像，第四个单元可以携带和输送实际的治疗药物。然后将所有单元(壳)连接到另一个树枝状大分子(核)上。通过这种方式，树枝状聚合物可以形成复杂的结构，实现抗癌的所有必要治疗方面。利用分子动力学模拟进行结构研究对于从树枝状大分子复合体中获得多功能器件至关重要。我们将通过这些计算研究预测设备的最佳参数，并减少相当大的化学试验台工作。 除了癌症治疗，树枝状大分子已被证明是优秀的基因传递载体。我们将使用树枝状大分子作为潜在的RNA干扰递送系统。一旦疗效得到证实，这种新型的RNA干扰就可以以细胞或器官特异性的方式发生。我们将在寡核苷酸和树枝状大分子之间进行分子动力学模拟，以找到这项任务的最佳条件。针对特定基因的寡核苷酸的序列特异性和热力学参数也将使用我们自己的算法进行计算。除了与癌症相关的基因外，目标基因还将是与抑郁症相关的基因。