Poly(ethylene glycol)-block-cationic polylactide nanocomplexes of differing charge density for gene delivery
Poly(ethylene glycol)-block-cationic polylactide nanocomplexes of differing charge density for gene delivery
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DOI：
10.1016/j.biomaterials.2013.08.063
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发表时间：
2013-12-01
期刊：
影响因子：
14
通讯作者：
Cheng, Chong
中科院分区：
文献类型：
--
作者：
Chen, Chih-Kuang;Jones, Charles H.;Cheng, Chong
通过烯丙基功能化的二嵌段共聚物前体的硫醇-烯功能化反应，合成了一种结构明确的含叔胺阳离子基团的聚乙二醇嵌段阳离子聚乳酸（PEG-b-CPLA）。随后研究了PEG-b-CPLAs作为可生物降解载体用于质粒DNA（pDNAs）递送的应用。通过由自发静电相互作用形成PEG-b-CPLA：pDNA纳米复合物，编码荧光素酶或增强型绿色荧光蛋白的pDNA被成功递送到四种生理上不同的细胞系（包括巨噬细胞、成纤维细胞、上皮细胞和干细胞）。当与阳性对照相比时，配制的纳米复合物表现出高水平的转染和低水平的细胞毒性和溶血。在各种聚合物：pDNA重量比的纳米复合物的电荷密度的生物物理表征揭示了表面电荷和基因递送之间的正相关性。具有高表面电荷密度的纳米复合物用于体外血清基因递送抑制测定，尽管血清水平高，但观察到有效的基因递送。总体而言，这些结果有助于阐明纳米复合物的电荷、大小和PEG化对在生理相关条件下递送核酸的影响。(C)2013爱思唯尔有限公司保留所有权利。
Representing a new type of biodegradable cationic block copolymer, well-defined poly(ethylene glycol)block-cationic polylactides (PEG-b-CPLAs) with tertiary amine-based cationic groups were synthesized by thiol-ene functionalization of an allyl-functionalized diblock precursor. Subsequently the application of PEG-b-CPLAs as biodegradable vectors for the delivery of plasmid DNAs (pDNAs) was investigated. Via the formation of PEG-b-CPLA:pDNA nanocomplexes by spontaneous electrostatic interaction, pDNAs encoding luciferase or enhanced green fluorescent protein were successfully delivered to four physiologically distinct cell lines (including macrophage, fibroblast, epithelial, and stem cell). Formulated nanocomplexes demonstrated high levels of transfection with low levels of cytotoxicity and hemolysis when compared to a positive control. Biophysical characterization of charge densities of nanocomplexes at various polymer:pDNA weight ratios revealed a positive correlation between surface charge and gene delivery. Nanocomplexes with high surface charge densities were utilized in an in vitro serum gene delivery inhibition assay, and effective gene delivery was observed despite high levels of serum. Overall, these results help to elucidate the influence of charge, size, and PEGylation of nanocomplexes upon the delivery of nucleic acids in physiologically relevant conditions. (C) 2013 Elsevier Ltd. All rights reserved.