Department of Chemistry, M. V. Lomonosov Moscow State University , 119991 Moscow, Russia.
Biomacromolecules. 2017 Mar 13;18(3):808-818. doi: 10.1021/acs.biomac.6b01678. Epub 2017 Mar 1.
Polycations are popular agents for nonviral delivery of DNA to mammalian cells. Adding hydrophobic, biodegradable, or cell-penetrating functions could help to improve their performance, which at present is below that of viral agents. A crucial first step in gene delivery is the complexation of the DNA. The characteristics of these "polyplexes" presumably influence or even determine the subsequent steps of membrane passage, intracellular traveling/DNA release, and nuclear uptake. Herein, polyplexes formed with linear poly(ethylenimine) (l-PEI) are compared to complexes generated with functionalized diblock copolymers. While l-PEI interacts only electrostatically with the DNA, interaction in the case of the diblock polymers may be mixed-mode. In certain cases, transfection efficiency improved when the polyplexes were formed in hypertonic solution. Moreover, whereas conventional PEI-based polyplexes enter the cells via endocytosis, at least one of the diblock agents seemed to promote entry via transient destabilization of the plasma membrane.
聚阳离子是将 DNA 非病毒递送至哺乳动物细胞的常用试剂。添加疏水性、可生物降解或细胞穿透性功能可以帮助提高其性能，目前其性能低于病毒试剂。基因传递的关键第一步是 DNA 的复合物形成。这些“聚合物”的特性可能会影响甚至决定随后的膜穿透、细胞内迁移/DNA 释放和核摄取步骤。本文比较了线性聚（亚乙基亚胺）（l-PEI）形成的聚合物与功能化二嵌段共聚物生成的复合物。虽然 l-PEI 仅与 DNA 静电相互作用，但二嵌段聚合物的相互作用可能是混合模式。在某些情况下，当聚合物在高渗溶液中形成时，转染效率会提高。此外，虽然基于常规 PEI 的聚合物通过胞吞作用进入细胞，但至少有一种二嵌段试剂似乎通过瞬时破坏质膜来促进进入。
