聚乙二醇化
转染
聚赖氨酸
小干扰RNA
基因传递
体内
PEG比率
细胞内
分子生物学
基因沉默
体外
材料科学
生物物理学
生物化学
化学
生物
聚乙二醇
基因
财务
生物技术
经济
作者
Haiyan Zhu,Chunyan Dong,Haiqing Dong,Tianbin Ren,Xuejun Wen,Jian Su,Yongyong Li
摘要
Polylysine with cleavable PEGylation and hydrophobic histidylation (mPEG-SS-Lysn-r-Hism) was designed and developed for efficient siRNA delivery and tumor therapy. mPEG-SS-Lysn-r-Hism was used to carry and deliver small interfering RNA (siRNA) for silencing endogenous vascular endothelial growth factor (VEGF) expression and inhibiting tumor growth in HepG2 tumor-bearing mice. In this gene vector, histidine(Bzl) was selected for hydrophobic histidylation for the proton sponge ability of the imidazole ring and hydrophobic benzyl group. Cleavable PEGylation was introduced for in vivo circulation as well as selective PEG detachment in response to intracellular reduction condition in order to release the genetic payload. PEG detachment induced gene release was supported by agarose gel electrophoresis retardation assay, undertaken in the intracellular relevant reduction condition. In vitro transfection evaluation of histidylated copolymers, using pEGFP as genetic model, indicated significantly higher GFP expression than unmodified counterparts, comparable to the gold standard PEI. The efficacy of hydrophobic histidylation was found to be pronounced in mesenchymal stem cells (MSCs). In vivo application of the VEGF-siRNA package by tailored mPEG-SS-Lysn-r-Hism showed distinct tumor suppression in terms of macroscopic tumor volume and molecular analysis.
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