title: A paradigm change: efficient transfection of human leukemia cells by stimuli-responsive multicompartment micelles.
abstract: 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.
authors.affiliation: Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena , Humboldtstrasse 10, 07743, Jena, Germany.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Rinkenauer
authors.forename: Anja
authors.initials: A
authors.lastname: Schallon
authors.forename: Ulrike
authors.initials: U
authors.lastname: Günther
authors.forename: Michael
authors.initials: M
authors.lastname: Wagner
authors.forename: Eva
authors.initials: E
authors.lastname: Betthausen
authors.forename: Ulrich S
authors.initials: US
authors.lastname: Schubert
authors.forename: Felix H
authors.initials: FH
authors.lastname: Schacher
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D001709:Biotechnology / Q000379:methods; D002070:Butadienes / Q000737:chemistry*; D002412:Cations; D045744:Cell Line, Tumor; D020285:Cryoelectron Microscopy; D005822:Genetic Vectors; D057809:HEK293 Cells; D006461:Hemolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019169:Jurkat Cells; D007938:Leukemia / Q000473:pathology*; D008689:Methacrylates / Q000737:chemistry; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology / Q000379:methods; D010957:Plasmids / Q000378:metabolism; D011108:Polymers / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry*; D014162:Transfection
chemical_list: D001672:Biocompatible Materials; D002070:Butadienes; D002412:Cations; D008689:Methacrylates; D008823:Micelles; D011108:Polymers; D011109:Polymethacrylic Acids; C000589847:polybutadiene-block-poly(methacrylic acid)-block-poly(2-(dimethylamino)ethyl methacrylate)