Systematically probing the bottom-up synthesis of AuPAMAM conjugates for enhanced transfection efficiency.
Systematically probing the bottom-up synthesis of AuPAMAM conjugates for enhanced transfection efficiency.
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DOI：
10.1186/s12951-016-0178-9
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发表时间：
2016-03-31
影响因子：
10.2
通讯作者：
Drezek RA
中科院分区：
文献类型：
--
作者：
Figueroa ER;Yan JS;Chamberlain-Simon NK;Lin AY;Foster AE;Drezek RA
金纳米粒子（AuNPs）由于其具有生物相容性、易于通过近共价金-硫键官能化以及表面等离子体光学特性等吸引人的理化特性，已显示出作为基因治疗载体支架的巨大前景。在此之前，我们合成了稳定的aunp -聚氨基酰胺（AuPAMAM）偶联物，并成功地在体外作为非病毒基因传递载体。在本研究中，我们系统地干扰了AuPAMAM偶联物的每个组分，并分析了其对转染效率的影响。由于AuPAMAM合成的模块化，自下而上的性质，我们能够探测制造过程的每个步骤。研究了各共轭参数与最终矢量函数之间的关系。通过改变PAMAM浓度、PAMAM核心化学、PAMAM末端化学和AuPAMAM偶联物的自组装单层组成，转染效率提高了四倍以上。这项工作表明AuPAMAM合成平台是一种很有前途的非病毒基因治疗方法，并强调了检查所有纳米技术混合材料中每个单独成分的作用的重要性。本文的在线版本（doi:10.1186/s12951-016-0178-9）包含补充材料，可供授权用户使用。
Gold nanoparticles (AuNPs) have shown great promise as scaffolds for gene therapy vectors due to their attractive physiochemical properties which include biocompatibility, ease of functionalization via the nearly covalent gold-sulfur dative bond, and surface plasmon optical properties. Previously, we synthesized stable AuNP-polyamidoamine (AuPAMAM) conjugates and showed their success in vitro as non-viral gene delivery vectors. In this study, we systematically perturbed each component of the AuPAMAM conjugates and analyzed the resulting effect on transfection efficiency. Due to the modular, bottom-up nature of the AuPAMAM synthesis, we were able to probe each step of the fabrication process. The relationship between each conjugation parameter and the function of the final vector were investigated. More than fourfold enhanced transfection efficiency was achieved by modifying the PAMAM concentration, PAMAM core chemistry, PAMAM terminus chemistry, and self-assembled monolayer composition of the AuPAMAM conjugates. This work suggest that AuPAMAM synthesis platform is a promising non-viral gene therapy approach and highlights the importance of inspecting the role of each individual constituent in all nanotechnology hybrid materials. The online version of this article (doi:10.1186/s12951-016-0178-9) contains supplementary material, which is available to authorized users.