DRUG AND GENE DELIVERY USING POLYMERS AND LIPOSOMES

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。 本研究的目的是利用多肽、聚合物或脂质体将其内容物输送到细胞质中，并对其转运机制进行表征，并利用内切体或溶酶体的低pH环境来催化聚合物/脂质体内容物进入细胞质。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进佐剂。一种方法是合成新型的多肽脂或多肽聚合物，它们可以经历低pH诱导的构象变化，导致引发膜融合的疏水序列的暴露。在本应用中，该多肽将附着在聚合物或脂质体的表面。第二种方法是合成可以进行pH依赖或酶修饰的前体药物，允许它们从溶酶体隔室排出。在这两种应用中，化学和物理方法都被用来设计更有效的药物输送系统，并确定其使用的限制。我们还在开发能够附着到细胞分子马达上的多肽，以将药物或基因引导到特定的位置，如细胞中的细胞核。

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.