title: Intracellular triggered release of DNA-quaternary ammonium polyplex by ultrasound.
abstract: 2-Methacryloyloxy ethyl trimethyl ammonium chloride (TMA) is a potent polymeric plasma DNA (pDNA) carrier. The present study shows that TMA/pDNA polyplexes could be internalized into cells efficiently, but could not mediate gene transfection on its own. The transfection process of TMA/pDNA polyplexes is turned on only when ultrasound (US) was applied 4-8h after incubating TMA/pDNA polyplexes with target cells (with a gene expression 1000 times that of the immediate US group). US is a widely used physical method for gene delivery; its transfection efficiency can be significantly enhanced when combined with cationic polymer vectors. Traditionally, US is given simultaneously with genetic materials, carriers and microbubbles to exert maximal efficacy. The unique on-off phenomenon of TMA/pDNA polyplexes, controlled by US exposure, was found to relate to the endosomal escape effect of US since the polyplexes colocalized well with the lysosome marker if no US was given or was given at inappropriate times. The proposed delivery system using US and TMA carriers has potential in many pharmaceutical applications requiring precise temporal and spatial release control.
authors.affiliation: Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Wei-Hao
authors.initials: WH
authors.lastname: Liao
authors.affiliation: Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan; Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Ming-Yen
authors.initials: MY
authors.lastname: Hsiao
authors.affiliation: Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Lo
authors.affiliation: R&D Center for Membrane Technology and Department of Chemical Engineering, Chung Yuan Christian University, Chong-Li, Taiwan.
authors.forename: Hui-Shan
authors.initials: HS
authors.lastname: Yang
authors.affiliation: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Ming-Kuan
authors.initials: MK
authors.lastname: Sun
authors.affiliation: Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan; Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Feng-Huei
authors.initials: FH
authors.lastname: Lin
authors.affiliation: R&D Center for Membrane Technology and Department of Chemical Engineering, Chung Yuan Christian University, Chong-Li, Taiwan. Electronic address: changyung0307@gmail.com.
authors.forename: Yung
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan; Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan; Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan. Electronic address: wenshiang@gmail.com.
authors.forename: Wen-Shiang
authors.initials: WS
authors.lastname: Chen
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D042541:Intracellular Space / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D014162:Transfection; D000069453:Ultrasonic Waves
chemical_list: D004337:Drug Carriers; D000644:Quaternary Ammonium Compounds; D004247:DNA
keywords: Cationic polymer; Endosomal escape; Gene transfection; Ultrasound