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用于小干扰RNA递送的树枝状肽两亲分子的基于结构的设计

Structure-Based Design of Dendritic Peptide Bolaamphiphiles for siRNA Delivery.

作者信息

Zeng Hanxiang, Johnson Mark E, Oldenhuis Nathan J, Tiambeng Timothy N, Guan Zhibin

机构信息

Department of Chemistry, University of California , Irvine, California 92697, United States.

出版信息

ACS Cent Sci. 2015 Sep 23;1(6):303-312. doi: 10.1021/acscentsci.5b00233. Epub 2015 Aug 14.

DOI:10.1021/acscentsci.5b00233
PMID:26436138
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4582325/
Abstract

Development of safe and effective delivery vectors is a critical challenge for the application of RNA interference (RNAi)-based biotechnologies. In this study we show the rational design of a series of novel dendritic peptide bolaamphiphile vectors that demonstrate high efficiency for the delivery of small interfering RNA (siRNA) while exhibiting low cytotoxicity and hemolytic activity. Systematic investigation into structure-property relationships revealed an important correlation between molecular design, self-assembled nanostructure, and biological activity. The unique bolaamphiphile architecture proved a key factor for improved complex stability and transfection efficiency. The optimal vector contains a fluorocarbon core and exhibited enhanced delivery efficiency to a variety of cell lines and improved serum resistance when compared to hydrocarbon analogues and lipofectamine RNAiMAX. In addition to introducing a promising new vector system for siRNA delivery, the structure-property relationships and "fluorocarbon effect" revealed herein offer critical insight for further development of novel materials for nucleic acid delivery and other biomaterial applications.

摘要

开发安全有效的递送载体是基于RNA干扰（RNAi）的生物技术应用面临的一项关键挑战。在本研究中，我们展示了一系列新型树枝状肽两亲性载体的合理设计，这些载体在递送小干扰RNA（siRNA）方面表现出高效率，同时具有低细胞毒性和溶血活性。对结构-性质关系的系统研究揭示了分子设计、自组装纳米结构和生物活性之间的重要关联。独特的两亲性结构被证明是提高复合物稳定性和转染效率的关键因素。与碳氢化合物类似物和脂质体RNAiMAX相比，最佳载体含有一个氟碳核心，对多种细胞系表现出更高的递送效率，并具有更好的血清耐受性。除了引入一种有前景的新型siRNA递送载体系统外，本文揭示的结构-性质关系和“氟碳效应”为进一步开发用于核酸递送的新型材料及其他生物材料应用提供了关键见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eaa/4858340/80a1ae29f9f8/oc-2015-00233g_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eaa/4858340/2725c627927b/oc-2015-00233g_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eaa/4858340/fe3c95ff0125/oc-2015-00233g_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eaa/4858340/25602c85ac8c/oc-2015-00233g_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eaa/4858340/dcfc1fd9e458/oc-2015-00233g_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eaa/4858340/80a1ae29f9f8/oc-2015-00233g_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eaa/4858340/2725c627927b/oc-2015-00233g_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eaa/4858340/fe3c95ff0125/oc-2015-00233g_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eaa/4858340/25602c85ac8c/oc-2015-00233g_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eaa/4858340/dcfc1fd9e458/oc-2015-00233g_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eaa/4858340/80a1ae29f9f8/oc-2015-00233g_0001.jpg

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