CQM - Centro de Química da Madeira, MMRG, Departamento de Química, Universidade da Madeira, Campus Universitário da Penteada, 9000-390 Funchal, Portugal.
J Control Release. 2010 May 21;144(1):55-64. doi: 10.1016/j.jconrel.2010.01.034. Epub 2010 Feb 6.
A new family of gene delivery vectors is synthesized consisting of a medium-size generation PAMAM dendrimer (generation 5, with amine termini) core randomly linked at the periphery to hydrophobic chains that vary in length (12 to 16 carbon alkyl chains) and number (from 4.2 to 9.7 in average). The idea subjacent to the present work is to join the advantages of the cationic nature of the dendrimer with the capacity of lipids to interact with biological membranes. Unlike other amphiphilic systems designed for the same purpose, where the hydrophobic and hydrophilic moieties coexist in opposite sides, the present vectors have a hydrophilic interior and a hydrophobic corona. The vectors are characterized in respect to their ability to neutralize, bind and compact plasmid DNA (pDNA). The complexes formed between the vectors and pDNA are analyzed concerning their size, zeta-potential, resistance to serum nucleases, capacity of being internalized by cells and transfection efficiency. These new vectors show a remarkable capacity for mediating the internalization of pDNA with minimum cytotoxicity, being this effect positively correlated with the -CH(2)- content present in the hydrophobic corona. Gene expression in MSCs, a cell type with relevancy in the regenerative medicine clinical context, is also enhanced using the new vectors but, in this case, the higher efficiency is shown by the vectors containing the smallest hydrophobic chains.
合成了一种新的基因传递载体家族，由一个中型代 PAMAM 树状大分子（第 5 代，带有胺末端）核心组成，该核心随机连接在疏水链的外围，疏水链的长度（12 至 16 个碳烷基链）和数量（平均为 4.2 至 9.7）各不相同。目前这项工作的想法是结合树突状大分子的阳离子性质和脂质与生物膜相互作用的能力。与其他为达到相同目的而设计的两亲性系统不同，这些系统的疏水和亲水部分存在于相反的两侧，而目前的载体具有亲水的内部和疏水的冠状物。这些载体的特征在于它们中和、结合和压缩质粒 DNA（pDNA）的能力。分析了载体与 pDNA 之间形成的复合物的大小、zeta 电位、对血清核酸酶的抗性、被细胞内化的能力和转染效率。这些新载体表现出介导 pDNA 内化的显著能力，同时具有最小的细胞毒性，这种效应与疏水冠状物中存在的-CH(2)-含量呈正相关。在与再生医学临床背景相关的间充质干细胞（MSCs）中，也增强了新载体的基因表达，但在这种情况下，含有最小疏水链的载体显示出更高的效率。
