Charge density and molecular weight of polyphosphoramidate gene carrier are key parameters influencing its DNA compaction ability and transfection efficiency.
Charge density and molecular weight of polyphosphoramidate gene carrier are key parameters influencing its DNA compaction ability and transfection efficiency.
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DOI：
10.1021/bm1009574
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发表时间：
2010-12-13
影响因子：
6.2
通讯作者：
Mao, Hai-Quan
中科院分区：
文献类型：
--
作者：
Ren, Yong;Jiang, Xuan;Pan, Deng;Mao, Hai-Quan
合成了一系列具有不同分子量 (MW) 和电荷密度的聚磷酸酰胺 (PPA)，并检查了它们的 DNA 压缩能力和转染效率。在三种不同细胞系（HeLa、HEK293 和 HepG2 细胞）中观察到 PPA/DNA 纳米颗粒的转染效率与 PPA 基因载体的分子量和净正电荷密度之间存在很强的相关性。 PPA载体的MW和/或净正电荷密度的增加产生了更高的DNA压实能力、具有更高表面电荷的更小的纳米颗粒以及针对盐和聚阴离子挑战的更高的复合物稳定性。纳米粒子的这些有利的物理化学特性导致转染效率提高。具有最高复合物稳定性的 PPA/DNA 纳米粒子表现出与 PEI/DNA 纳米粒子相当的转染效率，这可能是通过以更高的细胞摄取来补偿低缓冲能力，并为内溶酶体区室中的 DNA 提供更高水平的保护。转染效率的差异并不归因于载体之间细胞毒性的任何差异，因为所有纳米颗粒在转染条件下都显示出最低水平的细胞毒性。使用PPA作为模型系统，我们证明了聚合物基因载体转染效率的结构依赖性。这些结果为非病毒基因传递的纳米颗粒工程提供了更多见解。
A series of polyphosphoramidates (PPA) with different molecular weights (MWs) and charge densities were synthesized and examined for their DNA compaction ability and transfection efficiency. A strong correlation was observed between the transfection efficiency of PPA/DNA nanoparticles and the MW and net positive charge density of the PPA gene carriers in three different cell lines (HeLa, HEK293 and HepG2 cells). An increase in MW and/or net positive charge density of PPA carrier yielded higher DNA compaction capacity, smaller nanoparticles with higher surface charges and higher complex stability against challenges by salt and polyanions. These favorable physicochemical properties of nanoparticles led to enhanced transfection efficiency. PPA/DNA nanoparticles with the highest complex stability showed comparable transfection efficiency as PEI/DNA nanoparticles likely by compensating the low buffering capacity with higher cellular uptake and affording higher level of protection to DNA in endolysosomal compartment. The differences in transfection efficiency were not attributed by any difference in cytotoxicity among the carriers, as all nanoparticles showed minimal level of cytotoxicity under the transfection conditions. Using PPA as a model system, we demonstrated the structural dependence of transfection efficiency of polymer gene carrier. These results offer more insights into nanoparticle engineering for non-viral gene delivery.
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