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: 7601274
• 负责人: INHAN LEE
• 金额: $ 0.03万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601274
• 关键词: Algorithms; Architecture; Cells; Chemicals; Complex; Computer Retrieval of Information on Scientific Projects Database; Condition; Dendrimers; Devices; Funding; Gene Delivery; Gene Targeting; Genes; Grant; Image; Institution; Malignant Neoplasms; Mental Depression; Michigan; Modeling; Nanotechnology; Oligonucleotides; Organ; Polymers; RNA Interference; Research; Research Personnel; Resources; Source; Specificity; Structure; System; Therapeutic; Thermodynamics; United States National Institutes of Health; Universities; Work; abstracting; base; cancer therapy; computer studies; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 分子动力学模拟，树状大分子，肿瘤治疗，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。目前的计划是以确定的方式组装功能性树枝状聚合物，以制备具有多个功能的树枝状聚合物簇。 一个单元可以是具有靶向部分的树枝状聚合物，第二个单元是具有感测的树枝状聚合物，第三个单元是对肿瘤进行成像，第四个单元是携带和递送实际的治疗剂。然后所有单元（壳）连接到另一个树枝状聚合物（核）。以这种方式，树枝状聚合物可以形成复杂的结构，实现针对癌症的所有必要的治疗方面。使用MD模拟的结构研究在从树枝状聚合物复合物实现多功能装置中是至关重要的。我们将预测设备的最佳参数，并通过这些计算研究减少大量的化学实验室工作。 除了癌症治疗之外，树枝状聚合物已被证明用作优良的基因递送载体。我们将使用树枝状聚合物作为一个潜在的RNA干扰传递系统。一旦证实其有效性，这种新型的RNA干扰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聚合物之间进行MD模拟，以找到这项任务的最佳条件。还将使用我们自己的算法计算靶向某些基因的寡核苷酸的序列特异性和热力学参数。靶基因除了与癌症相关的基因外，还将是与抑郁症相关的基因。