Anionic Lipid, pH-Sensitive Liposome-Gold Nanoparticle Hybrids for Gene Delivery - Quantitative Research of the Mechanism

被引：30

作者：

Du, Baoji ^{[1
,2
]}

Tian, Li ^{[1
]}

Gu, Xiaoxiao ^{[1
]}

Li, Dan ^{[1
]}

Wang, Erkang ^{[1
]}

Wang, Jin ^{[1
,3
,4
]}

机构：

[1] Changchun Inst Appl Chem, State Key Lab Electroanalyt Chem, Changchun 130022, Jilin, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100039, Peoples R China

[3] Jilin Univ, Coll Phys, Changchun 130012, Jilin, Peoples R China

[4] SUNY Stony Brook, Dept Chem & Phys, Stony Brook, NY 11794 USA

来源：

SMALL | 2015年 / 11卷 / 19期

基金：

中国国家自然科学基金;

关键词：

anion-sensitive; gene delivery; gold nanoparticles; liposome; pH-sensitive;

D O I：

10.1002/smll.201402470

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Gene therapy is a potential method for treating a large range of diseases. Gene vectors are widely used in gene therapy for promoting the gene delivery efficiency to the target cells. Here, gold nanoparticles (AuNPs) coated with dimethyldioctadecylammonium bromide (DODAB)/dioleoylphosphatidylethanolamine (DOPE) are synthesized using a facile method for a new gene vector (DODAB/DOPE-AuNPs), which possess 3- and 1.5-fold higher transfection efficiency than those of DODAB-AuNPs and a commercial transfection agent, respectively. Meanwhile, it is nontoxic with concentrations required for effective gene delivery. Imaging and quantification studies of cellular uptake reveal that DOPE increases gene copies in cells, which may be attributed to the smaller size of AuNPs/DNA complexes. The dissociation efficiency of DNA from the endocytic pathway is quantified by incubating with different buffers and investigated directly in the cells. The results suggest that DOPE increases the internalization of AuNPs/DNA complexes and promotes DNA release from early endosomes for the vector is sensitive to the anionic lipid membrane and the decreasing pH along the endocytic pathway. The new vector contains the potential to be the new alternative as gene delivery vector for biomedical applications.

引用

页码：2333 / 2340

页数：8

共 54 条

[1] Sorgi F.L., Bhattacharya S., Huang L., Gene Ther., 4, (1997)
[2] Conner S.D., Schmid S.L., Nature, 422, (2003)
[3] Mochizuki S., Kanegae N., Nishina K., Kamikawa Y., Koiwai K., Masunaga H., Sakurai K., Biochim. Biophys. Acta-Biomembr., 1828, (2013)
[4] Rejman J., Oberle V., Zuhorn I.S., Hoekstra D., Biochem. J., 377, (2004)
[5] Nishiyama N., Iriyama A., Jang W.D., Miyata K., Itaka K., Inoue Y., Takahashi H., Yanagi Y., Tamaki Y., Koyama H., Kataoka K., Nat. Mater., 4, (2005)
[6] Bhattacharya S., Mandal S.S., Biochemistry, 37, (1998)
[7] Yu T., Liu X., Bolcato-Bellemin A.-L., Wang Y., Liu C., Erbacher P., Qu F., Rocchi P., Behr J.-P., Peng L., Angew. Chem. Int. Ed., 51, (2012)
[8] Sokolova V., Epple M., Angew. Chem. Int. Ed., 47, (2008)
[9] Hu W.W., Wang Z., Hollister S.J., Krebsbach P.H., Gene Ther., 14, (2007)
[10] Kay M.A., Glorioso J.C., Naldini L., Nat. Med., 7, (2001)

← 1 2 3 4 5 6 →