Nanodelivery System Laboratory, National Nanotechnology Center, National Science and Technology Development Agency, Pathum Thani, Thailand.
Nanodelivery System Laboratory, National Nanotechnology Center, National Science and Technology Development Agency, Pathum Thani, Thailand.
Carbohydr Polym. 2014 Apr 15;104:17-22. doi: 10.1016/j.carbpol.2013.12.077. Epub 2014 Jan 5.
Methylated N-pyridylmethyl chitosan chlorides (M-PyMeChCs) with a similar total degree of quaternization (DQT) and molecular weight but different N-pyridinium positions were synthesized by reductive amination and methylation, respectively. The effect of N-pyridinium positions on transfection efficiency and cytotoxicity was investigated in human hepatoma (Huh7) cell lines. The results revealed that M-PyMeChCs are able to form a complete complex formation with DNA since there is an N/P ratio of 5. The particle sizes of M-PyMeChCs/DNA nanopolyplexes were approximately 300 nm and indicated a positive charge. The morphology of these nanopolyplexes was found to be in a spherical shape which was investigated by using the transmission electron microscopy (TEM). The M4-PyMeChC/DNA nanopolyplexes showed highest in vitro transfection efficiency in Huh7 cells at N/P ratio of 20 compared to M2-PyMeChC/DNA and M3-PyMeChC/DNA nanopolyplexes. In comparison to M3-PyMeChC/DNA nanopolyplexes, M2-PyMeChC/DNA and M4-PyMeChC/DNA nanopolyplexes showed lower cytotoxicity in Huh7 cells. Our result demonstrated that N-pyridinium positions of M-PyMeChCs are related to transfection efficiency and cytotoxicity.
用还原胺化和甲基化法分别合成了总季铵化度（DQT）和分子量相似但 N-吡啶鎓位置不同的甲基化 N-吡啶基甲基壳聚糖氯化物（M-PyMeChCs）。在人肝癌（Huh7）细胞系中研究了 N-吡啶鎓位置对转染效率和细胞毒性的影响。结果表明，M-PyMeChCs 能够与 DNA 形成完整的复合物，因为存在 N/P 比为 5。M-PyMeChCs/DNA 纳米多聚物的粒径约为 300nm，呈正电荷。通过透射电子显微镜（TEM）发现这些纳米多聚物的形态呈球形。与 M2-PyMeChC/DNA 和 M3-PyMeChC/DNA 纳米多聚物相比，M4-PyMeChC/DNA 纳米多聚物在 N/P 比为 20 时在 Huh7 细胞中的体外转染效率最高。与 M3-PyMeChC/DNA 纳米多聚物相比，M2-PyMeChC/DNA 和 M4-PyMeChC/DNA 纳米多聚物在 Huh7 细胞中的细胞毒性较低。我们的结果表明，M-PyMeChCs 的 N-吡啶鎓位置与转染效率和细胞毒性有关。
