MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, PR China. yx
Colloids Surf B Biointerfaces. 2011 May 1;84(1):259-66. doi: 10.1016/j.colsurfb.2011.01.007. Epub 2011 Jan 13.
A facile approach for polymer gene carriers was used to construct hyaluronic acid (HA) shielding polyplexes due to the electrostatic interaction. By adding HA to PEI/DNA complexes, the ξ-potential of ternary polyplexes was changed from positive to negative. Spherical particles with diameter about 250nm were observed. Ethidium bromide exclusion assay indicated that the electrostatic complexation was loosened after addition of HA. However, DNA disassembly did not occur. The proper reason was that the intensity of negative charges was not strong enough to release DNA from the complexes in our experiment. The stability of PEI/DNA/HA polyplexes in physiological condition was improved and the cytotoxicity was reduced. Comparing with PEI/DNA polyplexes, the uptake and transfection efficiency of HA shielding polyplexes was lower for HEK293T cells probably due to the reduced adsorptive endocytosis, whereas it was higher for HepG2 cells due to HA receptor mediated endocytosis. This facile approach to constructing HA shielding polyplexes might have great potential application in non-viral gene delivery research and tumor therapy.
一种简便的聚合物基因载体方法被用于构建基于静电相互作用的透明质酸（HA）屏蔽的超分子聚合物。通过向 PEI/DNA 复合物中添加 HA，三元超分子聚合物的ξ电势从正变为负。观察到直径约为 250nm 的球形颗粒。溴化乙锭排除试验表明，添加 HA 后静电复合物的结合被松弛，但 DNA 并未解组装。适当的原因是在我们的实验中，负电荷的强度不够强，无法从复合物中释放 DNA。PEI/DNA/HA 超分子聚合物在生理条件下的稳定性得到提高，细胞毒性降低。与 PEI/DNA 超分子聚合物相比，HA 屏蔽超分子聚合物对 HEK293T 细胞的摄取和转染效率较低，可能是由于吸附性内吞作用减少所致，而对 HepG2 细胞的摄取和转染效率较高，这可能是由于 HA 受体介导的内吞作用所致。这种简便的方法构建 HA 屏蔽超分子聚合物可能在非病毒基因传递研究和肿瘤治疗中有很大的潜在应用。
