A linear-dendritic cationic vector for efficient DNA grasp and delivery

作者：Yang Bin; Sun Yun xia; Yi Wen jie; Yang Juan; Liu Chen wei; Cheng Han; Feng Jun^*; Zhang Xian zheng; Zhuo Ren xi

来源：Acta Biomaterialia, 2012, 8(6): 2121-2132.

DOI：10.1016/j.actbio.2012.02.013

• Endosomal buffering
• Gene delivery
• Methoxyl-poly(ethylene glycol)-dendritic polyglycerol-g-tris(2-aminoethyl)amine (mPEG-DPG-g-TAEA)
• Cationic vector
• Protein adsorption

This paper presents an attempt to design an efficient and biocompatible cationic gene vector via structural optimization that favors the efficient utilization of amine groups for DNA condensation. To this end, a linear-dendritic block copolymer of methoxyl-poly(ethylene glycol)-dendritic polyglycerol-graft-tris(2-aminoethyl)amine (mPEG-DPG-g-TAEA) was prepared with specially designed multiple functions including strong DNA affinity, endosomal buffering and expected serum-tolerance. Based on the transfection in serum-free and serum-conditioned media, the influences of the polymer structures including the degree of polymerization of DPG and TAEA substitution degree were explored. As compared to polyethylenimine (M-w = 5 kDa) (PEI5k) with similar molecular weight and higher amine density, mPEG-DPG-g-TAEA displayed comparably high DNA affinity due to the special linear-dendritic architecture. Consequently, at very low N/P ratio. mPEG-DPG-g-TAEA vectors could mediate efficient in vitro luciferase expression at levels that are comparable with or even superior to the commercially available Lipofectamine (TM) 2000, while being apparently higher than PEI5k. The designed vectors exhibit considerably higher cell biocompatibility and better resistance against bovine serum albumin adsorption than PEI5k. The stability of the complexes on coincubation with heparin was found to be largely dependent on the polymer structure. As concluded from the comparative transfection study in the absence/presence of chloroquine, it is likely that the polycation itself could produce Endosomal buffering. This linear-dendritic vector shows promising potential for the application of gene delivery.

• 出版日期2012-7
• 单位武汉大学