A Paradigm Change: Efficient Transfection of Human Leukemia Cells by Stimuli-Responsive Multicompartment Micelles

被引：61

作者：

Rinkenauer, Alexandra C. ^{[1
,2
]}

Schallon, Anja ^{[1
,2
]}

Guenther, Ulrike ^{[1
,2
]}

Wagner, Michael ^{[1
,2
]}

Betthausen, Eva ^{[3
]}

Schubert, Ulrich S. ^{[1
,2
]}

Schacher, Felix H. ^{[1
,2
]}

机构：

[1] Univ Jena, Lab Organ & Macromol Chem IOMC, D-07743 Jena, Germany

[2] Univ Jena, JCSM, D-07743 Jena, Germany

[3] Univ Bayreuth, Bayreuth Ctr Colloids & Interfaces, D-95440 Bayreuth, Germany

来源：

ACS NANO | 2013年 / 7卷 / 11期

关键词：

multicompartment micelles; interpolyelectrolyte complexes; nonviral gene transfection; polyplexes; human leukemia cells; NONVIRAL GENE DELIVERY; CONFORMATIONAL-CHANGES; MOLECULAR-WEIGHT; CELLULAR UPTAKE; DNA; SIRNA; POLYETHYLENIMINE; NANOPARTICLES; POLYPLEX; PEGYLATION;

D O I：

10.1021/nn402072d

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The controlled nonviral delivery of genetic material using cationic polymers into cells has been of interest during the past three decades, yet the ideal delivery agent featuring utmost transfection efficiency and low cytotoxicity still has to be developed. Here, we demonstrate that multicompartment micelles from stimuli-responsive triblock terpolymers, polybutadiene-block-poly(methacrylic acid)-block-poly(2-(dimethylamino)ethyl methacrylate) (BMAAD), are promising candidates. The structures exhibit a patchy shell, consisting of amphiphilic (interpolyelectrolyte complexes, MAA and D) and cationic patches (excess D), generating a surface reminiscent to those of certain viruses and capable of undergoing pH-dependent changes in charge stoichiometry. After polyplex formation with plasmid DNA, superior transfection efficiencies can be reached for both adherent cells and human leukemia cells. Compared to the gold standard PEI, remarkable improvements and a number of advantages were identified for this system, including increased cellular uptake and an improved release of the genetic material, accompanied by fast and efficient endosomal escape. Furthermore, high sedimentation rates might be beneficial regarding in vitro applications.

引用

页码：9621 / 9631

页数：11

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