Stearylated INF7 peptide enhances endosomal escape and gene expression of PEGylated nanoparticles both in vitro and in vivo
Stearylated INF7 peptide enhances endosomal escape and gene expression of PEGylated nanoparticles both in vitro and in vivo
复制标题
DOI：
10.1002/jps.22807
复制
发表时间：
2012-02-01
影响因子：
3.8
通讯作者：
Harashima, Hideyoshi
中科院分区：
文献类型：
--
作者：
El-Sayed, Ayman;Masuda, Tomoya;Harashima, Hideyoshi
我们之前报道过一种硬脂酰化的INF7肽（str - INF7），它以一种不依赖融合的方式增强了包裹质粒DNA（pDNA）的八精氨酸（R8）修饰的脂质体颗粒的内涵体逃逸。本研究检测了这种肽衍生物是否能增强包裹pDNA的聚乙二醇化脂质体的内涵体逃逸和基因表达。我们使用一种聚乙二醇化的、R8修饰的多功能包膜型纳米装置（R8MEND）作为聚乙二醇化脂质体的模型。将聚乙二醇2000（PEG2000）连接到两种不同的锚定物，即二硬脂酰磷脂酰乙醇胺（DSPE - PEG）或二肉豆蔻酰磷脂酰乙醇胺（DMPE - PEG）上，用于在存在或不存在两种不同浓度的str - INF7的情况下修饰R8MEND。用str - INF7修饰聚乙二醇化的R8MEND后，在HeLa细胞中荧光素酶基因的表达水平分别比未修饰的MEND在DSPE - PEG和DMPE - PEG情况下的相应值高73倍和24倍。通过共聚焦激光扫描显微镜证实，str - INF7改善了聚乙二醇化R8MEND的内涵体逃逸。此外，在小鼠静脉注射后，用str - INF7修饰使经DSPE - PEG和DMPE - PEG修饰的R8MEND的肝脏基因表达分别增强了95倍和1885倍。总之，这些数据表明，str - INF7即使对于包裹pDNA的聚乙二醇化脂质体也是一种增强内涵体逃逸的有用工具。（C）2011威利期刊公司和美国药剂师协会《药物科学杂志》101:879 - 882，2012
We previously reported on a stearylated INF7 peptide (str-INF7), which enhances the endosomal escape of an octaarginine (R8)-modified liposomal particle encapsulating plasmid DNA (pDNA) in a fusion-independent manner. This study examined whether this peptide derivative enhanced the endosomal escape and gene expression of PEGylated liposomes encapsulating pDNA. We used a PEGylated, R8-modified multifunctional envelope-type nanodevice (R8MEND) as a model for PEGylated liposomes. Polyethylene glycol 2000 (PEG2000) attached to two different anchors, distearoylphosphatidylethanolamine (DSPEPEG) or dimyristoylphosphatidylethanolamine (DMPEPEG), was used to modify the R8MEND in the presence or absence of two different concentrations of str-INF7. Modification of the PEGylated R8MEND with str-INF7 resulted in luciferase gene expression levels in HeLa cells that were 73-fold and 24-fold higher than the corresponding value for an unmodified MEND in the case of DSPEPEG and DMPEPEG, respectively. The endosomal escape of the PEGylated R8MEND was improved by str-INF7, as confirmed by confocal laser scanning microscopy. Furthermore, modification with str-INF7 enhanced the hepatic gene expression of the R8MEND modified with DSPEPEG and DMPEPEG by 95-fold and 1885-fold, respectively, after intravenous injection in mice. Collectively, these data demonstrate that str-INF7 can be a useful device for enhancing the endosomal escape even for PEGylated liposomes encapsulating pDNA. (C) 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:879882, 2012