Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China.
Acta Biomater. 2010 Nov;6(11):4285-95. doi: 10.1016/j.actbio.2010.06.016. Epub 2010 Jun 18.
Novel functional biodegradable gene vectors, poly(L-succinimide)-g-polyethylenimines-g-poly(ethylene glycol) (PSI-g-PEI-g-PEGs) were synthesized by conjugating methoxy poly(ethylene glycol) (mPEG, M(w)=750 Da) to PEI segments (M(w)=800 Da) of PSI-g-PEI. The physicochemical properties of PSI-g-PEI-g-PEGs, including buffering capability, pDNA binding ability, cytotoxicity, zeta potential and the particle size of polymer/pDNA complexes, were explored. The influence of PEGylation was discussed based on a comparative study of PSI-g-PEI-g-PEGs, PSI-g-PEI and PEI25k (M(w)=25 kDa). SEM images revealed that PSI-g-PEI-g-PEG/pDNA particles have a regular shape with the diameter ranging from 70 to 170 nm. PEGylation could suppress the aggregation occurrence between complexes, resulting in a reduction of the polymer/pDNA complex size. PSI-g-PEI-g-PEGs exhibited remarkably lower cytotoxicity compared to PSI-g-PEI and PEI25k. In 293T and HeLa cells, the obtained PSI-g-PEI-g-PEGs showed very high transfection efficiency compared to PEI25k. Fluorescent confocal microscopy demonstrated that PSI-g-PEI-g-PEGs could effectively transport pGL-3 plasmids into the nuclei of HeLa cells. Taking into account the continued high transfection efficacy and decreased toxicity after PEG modification, PSI-g-PEI-g-PEGs show great potential as the non-viral vectors for gene transfection.
新型功能可生物降解基因载体聚（L-琥珀酰亚胺）-g-聚亚乙基亚胺-g-聚乙二醇（PSI-g-PEI-g-PEGs）通过将甲氧基聚乙二醇（mPEG，Mw=750 Da）接枝到PSI-g-PEI 的聚亚乙基亚胺（PEI）段（Mw=800 Da）上合成。研究了 PSI-g-PEI-g-PEGs 的理化性质，包括缓冲能力、pDNA 结合能力、细胞毒性、Zeta 电位和聚合物/pDNA 复合物的粒径。通过 PSI-g-PEI-g-PEGs、PSI-g-PEI 和 PEI25k（Mw=25 kDa）的对比研究，探讨了 PEG 化的影响。SEM 图像显示 PSI-g-PEI-g-PEG/pDNA 颗粒具有规则的形状，粒径范围为 70-170nm。PEG 化可以抑制复合物之间的聚集，从而减小聚合物/pDNA 复合物的粒径。与 PSI-g-PEI 和 PEI25k 相比，PSI-g-PEI-g-PEG 表现出显著降低的细胞毒性。在 293T 和 HeLa 细胞中，与 PEI25k 相比，所得到的 PSI-g-PEI-g-PEG 表现出非常高的转染效率。荧光共聚焦显微镜显示 PSI-g-PEI-g-PEG 可以有效地将 pGL-3 质粒运送到 HeLa 细胞的细胞核中。考虑到 PEG 修饰后持续的高转染效率和降低的毒性，PSI-g-PEI-g-PEG 作为基因转染的非病毒载体具有很大的潜力。
