MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China.
Carbohydr Polym. 2014 Jan 30;101:104-12. doi: 10.1016/j.carbpol.2013.09.053. Epub 2013 Sep 19.
The ideal gene polyplexes should have a subtle balance between polyplex stability to protect DNA against nucleases, and polyplex instability to permit DNA dissociation inside cells. In this research, low molecular weight trimethylated chitosan was chemically modified with poly(ε-caprolactone). Owing to the amphiphilic character, trimethylated chitosan-graft-poly(ε-caprolactone) (TMC-g-PCL) formed nanoparticles in aqueous media. TMC-g-PCL nanoparticles could effectively condense pDNA into polyplexes about 200 nm in size. The TMC-g-PCL/DNA polyplexes were stable in physiological salt condition and showed high uptake efficiency probably due to the increasing cell membrane-carrier interaction as a result of hydrophobic modification. However, the high degree of quaternization influenced the buffer capacity of TMC-g-PCL and led to a reduction in the release from the lysosomes. By adding chloroquine to exclude the limitation of lysosome escape, the transfection efficiency of TMC-g-PCL/DNA polyplexes was similar to that of PEI/DNA polyplexes. This study demonstrated the potential of TMC-g-PCL/DNA nanoparticles as an efficient carrier for gene delivery.
理想的基因复合物应该在复合物稳定性和细胞内 DNA 解离不稳定性之间取得微妙的平衡。在这项研究中，低分子量的三甲基壳聚糖经化学修饰与聚（ε-己内酯）接枝。由于具有两亲性，三甲基壳聚糖接枝聚（ε-己内酯）（TMC-g-PCL）在水介质中形成纳米粒子。TMC-g-PCL 纳米粒子可以有效地将 pDNA 凝聚成约 200nm 大小的复合物。TMC-g-PCL/DNA 复合物在生理盐条件下稳定，并且由于疏水性修饰导致细胞内载体相互作用增加，从而具有较高的摄取效率。然而，高程度的季铵化影响了 TMC-g-PCL 的缓冲能力，并导致从溶酶体中的释放减少。通过添加氯喹排除溶酶体逃逸的限制，TMC-g-PCL/DNA 复合物的转染效率与 PEI/DNA 复合物相似。这项研究证明了 TMC-g-PCL/DNA 纳米粒子作为基因传递有效载体的潜力。
