PMID- 24147450 OWN - NLM STAT- MEDLINE DCOM- 20140725 LR - 20131126 IS - 1936-086X (Electronic) IS - 1936-0851 (Linking) VI - 7 IP - 11 DP - 2013 Nov 26 TI - A paradigm change: efficient transfection of human leukemia cells by stimuli-responsive multicompartment micelles. PG - 9621-31 LID - 10.1021/nn402072d [doi] AB - 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. FAU - Rinkenauer, Alexandra C AU - Rinkenauer AC AD - Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena , Humboldtstrasse 10, 07743, Jena, Germany. FAU - Schallon, Anja AU - Schallon A FAU - Gunther, Ulrike AU - Gunther U FAU - Wagner, Michael AU - Wagner M FAU - Betthausen, Eva AU - Betthausen E FAU - Schubert, Ulrich S AU - Schubert US FAU - Schacher, Felix H AU - Schacher FH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131028 PL - United States TA - ACS Nano JT - ACS nano JID - 101313589 RN - 0 (Biocompatible Materials) RN - 0 (Butadienes) RN - 0 (Cations) RN - 0 (Methacrylates) RN - 0 (Micelles) RN - 0 (Polymers) RN - 0 (Polymethacrylic Acids) RN - 0 (polybutadiene-block-poly(methacrylic acid)-block-poly(2-(dimethylamino)ethyl methacrylate)) SB - IM MH - Biocompatible Materials/chemistry MH - Biotechnology/methods MH - Butadienes/*chemistry MH - Cations MH - Cell Line, Tumor MH - Cryoelectron Microscopy MH - Genetic Vectors MH - HEK293 Cells MH - Hemolysis MH - Humans MH - Hydrogen-Ion Concentration MH - Jurkat Cells MH - Leukemia/*pathology MH - Methacrylates/chemistry MH - *Micelles MH - Microscopy, Electron, Transmission MH - Nanotechnology/methods MH - Plasmids/metabolism MH - Polymers/chemistry MH - Polymethacrylic Acids/*chemistry MH - Transfection EDAT- 2013/10/24 06:00 MHDA- 2014/07/26 06:00 CRDT- 2013/10/24 06:00 PHST- 2013/10/24 06:00 [entrez] PHST- 2013/10/24 06:00 [pubmed] PHST- 2014/07/26 06:00 [medline] AID - 10.1021/nn402072d [doi] PST - ppublish SO - ACS Nano. 2013 Nov 26;7(11):9621-31. doi: 10.1021/nn402072d. Epub 2013 Oct 28.