DRUG AND GENE DELIVERY USING POLYMERS AND LIPOSOMES

使用聚合物和脂质体进行药物和基因递送

• 批准号: 8363723
• 负责人: FRANCIS C. SZOKA
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363723
• 关键词: Adjuvant; Cell Nucleus; Cells; Chemicals; Cytoplasm; Drug Delivery Systems; Endosomes; Environment; Funding; Gene Delivery; Genes; Goals; Grant; Human; Lipids; Liposomes; Location; Lysosomes; Malignant Neoplasms; Mass Spectrum Analysis; Membrane Fusion; Modification; Molecular Motors; National Center for Research Resources; Peptides; Pharmaceutical Preparations; Polymers; Principal Investigator; Prodrugs; Research; Research Infrastructure; Resources; Source; Surface; United States National Institutes of Health; Vaccines; cost; design; improved; novel

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. The goal of this research is to use peptides, polymers or liposomes to deliver their contents into the cytoplasm of cells, to characterize the mechanism of delivery and to exploit the low pH environment of the endosome or lysosome to catalyze delivery of polymer/liposomal contents into cytoplasm. Another goal of this research is to develop gene and drug approaches to treat cancer. A third goal of our research is to develop improved adjuvants to use in human vaccines. One approach is to synthesize novel peptide lipids or peptide polymers that can undergo a low pH induced conformational change that results in the exposure of hydrophobic sequences that initiate membrane fusion. The peptide would be attached to the surface of the polymer or liposome in this application. A second approach is to synthesize prodrugs that can undergo either a pH dependent or enzymatic modification which permits their efflux from the lysosomal compartment. In either of these applications chemical and physical approaches are being used to design more efficient drug delivery systems and to determine the limitations to their use. We are also developing peptides that can attach to cellular molecular motors to direct the drug or gene to particular locations such as the nucleus in the cell.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 本研究的目的是使用肽、聚合物或脂质体将其内容物递送到细胞的细胞质中，表征递送机制，并利用内体或溶酶体的低pH环境来催化聚合物/脂质体内容物递送到细胞质中。 这项研究的另一个目标是开发治疗癌症的基因和药物方法。我们研究的第三个目标是开发用于人类疫苗的改良佐剂。一种方法是合成新的肽脂质或肽聚合物，其可以经历低pH诱导的构象变化，导致引发膜融合的疏水序列的暴露。 在本申请中，肽将连接到聚合物或脂质体的表面。 第二种方法是合成前药，所述前药可以经历pH依赖性或酶促修饰，这允许它们从溶酶体区室流出。 在这些应用中的任一个中，化学和物理方法被用于设计更有效的药物递送系统并确定其使用的限制。我们还在开发肽，它可以附着在细胞分子马达上，将药物或基因引导到细胞核等特定位置。