Polyethyleneimine-lipid conjugate-based pH-sensitive micellar carrier for gene delivery.
Polyethyleneimine-lipid conjugate-based pH-sensitive micellar carrier for gene delivery.
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DOI：
10.1016/j.biomaterials.2011.11.088
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发表时间：
2012-05
期刊：
影响因子：
14
通讯作者：
Torchilin, Vladimir P.
中科院分区：
文献类型：
--
作者：
Sawant, Rupa R.;Sriraman, Shravan Kumar;Navarro, Gemma;Biswas, Swati;Dalvi, Riddhi A.;Torchilin, Vladimir P.
用二油酰磷脂酰乙醇胺（PE）修饰低分子量聚乙烯亚胺（PEI 1.8kDa）以形成作为转染载体研究的PEI-PE缀合物。优化后的PEI-PE/pDNA复合物在N/P比为16时，粒径为225 nm，表面电荷为+31 mV，可保护pDNA免受DNase I的作用。PEI-PE缀合物具有约34 μg/ml的临界胶束浓度（CMC），并且与高分子量PEI（PEI 25 kDa）相比，如用B16-F10黑素瘤细胞测试的，没有表现出毒性。用PEI-PE/pEGFP复合物转染的B16-F10细胞显示出比用PEI-1.8或PEI-25载体更高的蛋白质表达水平。用YOYO 1标记的pEGFP制备的复合物证实了与PEI-1.8和PEI-25相比，用PEI-PE增强的质粒递送。PEI-PE/pDNA复合物还与不同量的胶束形成材料聚乙二醇（PEG）-PE混合以改善生物相容性。所得颗粒表现出中性表面电荷，耐盐诱导的聚集，和良好的转染活性在血清的存在下，在完全培养基。低pH可降解的PEG-腙-PE的使用产生了对与相对酸性的肿瘤环境一致的pH变化敏感的具有转染活性的颗粒。
A low molecular weight polyethyleneimine (PEI 1.8 kDa) was modified with dioleoylphosphatidylethanolamine (PE) to form the PEI-PE conjugate investigated as a transfection vector. The optimized PEI-PE/pDNA complexes at an N/P ratio of 16 had a particle size of 225 nm, a surface charge of +31 mV, and protected the pDNA from the action of DNase I. The PEI-PE conjugate had a critical micelle concentration (CMC) of about 34 μg/ml and exhibited no toxicity compared to a high molecular weight PEI (PEI 25 kDa) as tested with B16-F10 melanoma cells. The B16-F10 cells transfected with PEI-PE/pEGFP complexes showed protein expression levels higher than with PEI-1.8 or PEI-25 vectors. Complexes prepared with YOYO 1-labeled pEGFP confirmed the enhanced delivery of the plasmid with PEI-PE compared to PEI-1.8 and PEI-25. The PEI-PE/pDNA complexes were also mixed with various amounts of micelle-forming material, polyethylene glycol (PEG)-PE to improve biocompatibility. The resulting particles exhibited a neutral surface charge, resistance to salt-induced aggregation, and good transfection activity in the presence of serum in complete media. The use of the low-pH-degradable PEG-hydrazone-PE produced particles with transfection activity sensitive to changes in pH consistent with the relatively acidic tumor environment.
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