Hao Junguo, Sha Xianyi, Tang Yuanjia, Jiang Ye, Zhang Zhiwen, Zhang Wei, Li Yajuan, Fang Xiaoling
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China.
Arch Pharm Res. 2009 Jul;32(7):1045-54. doi: 10.1007/s12272-009-1710-3. Epub 2009 Jul 31.
Third generation cationic dendritic polymeric polypropyleneimine (PPI) was modified by Pluronic P123 and investigated for gene delivery. The cytotoxicity of P123-PPI was evaluated by the MTT assay and shown to be much lower than that of PPI alone. P123-PPI and PPI can both condense plasmid DNA into nanoparticles with a size of approximately 100 nm and a zeta potential of about 15 mV at the N/P ratio 20:1. The nanoparticles can protect plasmid DNA from being digested by DNase I at a concentration of 0.4 U/microg DNA. The nanoparticles were resistant to dissociation induced by 50% fetal bovine serum and 75 microg/mL sodium heparin. The transfection efficiency of SPC-A1 cells using P123-PPI/DNA nanoparticles was much higher than the transfection utilizing PPI/DNA nanoparticles. The addition of free P123 during the preparation of P123-PPI/DNA nanoparticles could significantly enhance the transfection efficiency in the presence of 10% fetal bovine serum. Therefore, P123-PPI/DNA complex nanoparticles may be a safe, efficient and promising cationic conjugate for gene delivery.
第三代阳离子树枝状聚合物聚丙烯亚胺（PPI）用普朗尼克P123进行了修饰，并对其基因传递性能进行了研究。通过MTT法评估了P123-PPI的细胞毒性，结果表明其细胞毒性远低于单独的PPI。在N/P比为20:1时，P123-PPI和PPI都能将质粒DNA浓缩成大小约为100 nm、ζ电位约为15 mV的纳米颗粒。在DNA浓度为0.4 U/μg时，这些纳米颗粒能保护质粒DNA不被DNase I消化。这些纳米颗粒对50%胎牛血清和75 μg/mL肝素钠诱导的解离具有抗性。使用P123-PPI/DNA纳米颗粒对SPC-A1细胞的转染效率远高于使用PPI/DNA纳米颗粒的转染效率。在制备P123-PPI/DNA纳米颗粒过程中添加游离的P123，在存在10%胎牛血清的情况下可显著提高转染效率。因此，P123-PPI/DNA复合纳米颗粒可能是一种用于基因传递的安全、高效且有前景的阳离子共轭物。
