聚糖聚合物对聚（L-赖氨酸）理化性质和基因传递生物学性质的修饰作用。

Glycopolymer modification on physicochemical and biological properties of poly(L-lysine) for gene delivery.

机构信息

Key Laboratory of Functional Polymer Materials (Nankai University), Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Tianjin, China.

出版信息

Int J Biol Macromol. 2012 May 1;50(4):965-73. doi: 10.1016/j.ijbiomac.2012.02.021. Epub 2012 Feb 25.

DOI:10.1016/j.ijbiomac.2012.02.021

PMID:22390846

Abstract

Poly(L-lysine) (PLL) has excellent plasmid DNA (pDNA) condensation capacity. However, the relatively high cytotoxicity and low transfection efficiency limit its application as gene delivery vectors. Here, well-defined glycopolymers are synthesized by reversible addition fragmentation transfer polymerization and grafted onto PLL to improve the gene delivery performance. After glycopolymer modification, PLL shows reduced cytotoxicity. By regulating the glycopolymer length and amino group substitution degree, the glycopolymer modified PLL can condense pDNA with proper strength, protect the condensed pDNA from degradation and release them in time. Transfection with NIH3T3 and HepG2 cells shows that the glycopolymer modified PLL has improved transfection efficiencies. The low cytotoxicity, effective pDNA protection and enhanced transfection efficiencies indicate that glycopolymer modification would be an effective strategy to improve the polycation properties for gene delivery.

摘要

聚 L-赖氨酸 (PLL) 具有优异的质粒 DNA (pDNA) 凝聚能力。然而，相对较高的细胞毒性和较低的转染效率限制了其作为基因传递载体的应用。在这里，通过可逆加成-断裂链转移聚合反应合成了结构明确的糖聚合物，并将其接枝到 PLL 上，以提高基因传递性能。糖聚合物修饰后，PLL 的细胞毒性降低。通过调节糖聚合物的长度和氨基取代度，可以使糖聚合物修饰的 PLL 具有适当的凝聚 pDNA 的强度，保护凝聚的 pDNA 免受降解并及时释放。用 NIH3T3 和 HepG2 细胞进行转染表明，糖聚合物修饰的 PLL 提高了转染效率。低细胞毒性、有效保护 pDNA 和增强的转染效率表明，糖聚合物修饰是改善聚阳离子性质用于基因传递的有效策略。