Kim Tae Hee, Cook Seung Eun, Arote Rohidas B, Cho Myung-Haing, Nah Jae Woon, Choi Yun Jaie, Cho Chong Su
School of Agricultural Biotechnology, Seoul National University, Seoul 151-921, South Korea.
Macromol Biosci. 2007 May 10;7(5):611-9. doi: 10.1002/mabi.200600245.
Polyethylenimine (PEI) is a well-known cationic polymer which has high transfection efficiency due to its buffering effect. However, nondegradability, cytotoxicity, aggregation, and short-circulation time in vivo still need to be overcome for a successful gene delivery. Degradable, hyperbranched poly(ester amine)s (PEAs) based on poloxamer diacrylate and low molecular weight branched PEI, were successfully synthesized and evaluated as a nonviral gene carrier. The PEAs were obtained in significant yields through Michael type addition reaction of diacrylate monomers and low molecular weight branched PEI. Analysis of degradation products by the reduction in molecular weight demonstrated that PEAs degrade in a controlled fashion. The PEA showed good DNA binding ability and the sizes of complexes under physiological condition were below 150 nm, implicating its potential for intracellular delivery. It showed lower cytotoxicity in three different cell lines (A549, 293T, and HepG2) compared with PEI 25K. PEAs showed much higher transfection efficiencies in three cell lines compared with PEI 25K and PEI 1.8K, and revealed little serum dependency in A549 cell line when the content of poloxamer in the PEA was increased up to 30%.
聚乙烯亚胺（PEI）是一种著名的阳离子聚合物，因其缓冲作用而具有高转染效率。然而，要成功实现基因递送，仍需克服其不可降解性、细胞毒性、聚集性以及在体内的短循环时间等问题。基于泊洛沙姆二丙烯酸酯和低分子量支化PEI成功合成了可降解的超支化聚（酯胺）（PEA），并将其作为非病毒基因载体进行了评估。通过二丙烯酸酯单体与低分子量支化PEI的迈克尔型加成反应，以较高产率获得了PEA。通过分子量降低对降解产物进行分析表明，PEA以可控方式降解。PEA表现出良好的DNA结合能力，在生理条件下复合物的尺寸低于150 nm，这意味着其具有细胞内递送的潜力。与25K的PEI相比，它在三种不同细胞系（A549、293T和HepG2）中表现出较低的细胞毒性。与25K的PEI和PEI 1.8K相比，PEA在三种细胞系中表现出更高的转染效率，并且当PEA中泊洛沙姆的含量增加到30%时，在A549细胞系中显示出几乎没有血清依赖性。
