Intracellular triggered release of DNA-quaternary ammonium polyplex by ultrasound

Wei-Hao Liao; Ming-Yen Hsiao; Chia-Wen Lo; Hui-Shan Yang; Ming-Kuan Sun; Feng-Huei Lin; Yung Chang; Wen-Shiang Chen

doi:10.1016/j.ultsonch.2016.11.002

Intracellular triggered release of DNA-quaternary ammonium polyplex by ultrasound

Ultrason Sonochem. 2017 May:36:70-77. doi: 10.1016/j.ultsonch.2016.11.002. Epub 2016 Nov 4.

Authors

Wei-Hao Liao¹, Ming-Yen Hsiao², Chia-Wen Lo¹, Hui-Shan Yang³, Ming-Kuan Sun⁴, Feng-Huei Lin⁵, Yung Chang⁶, Wen-Shiang Chen⁷

Affiliations

¹ Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
² 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.
³ R&D Center for Membrane Technology and Department of Chemical Engineering, Chung Yuan Christian University, Chong-Li, Taiwan.
⁴ Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan.
⁵ Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan; Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan.
⁶ R&D Center for Membrane Technology and Department of Chemical Engineering, Chung Yuan Christian University, Chong-Li, Taiwan. Electronic address: changyung0307@gmail.com.
⁷ 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.

PMID: 28069241
DOI: 10.1016/j.ultsonch.2016.11.002

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.

Keywords: Cationic polymer; Endosomal escape; Gene transfection; Ultrasound.

MeSH terms

Animals
DNA / chemistry*
DNA / genetics
DNA / metabolism
Drug Carriers / chemistry*
Drug Liberation*
Intracellular Space / metabolism*
Mice
NIH 3T3 Cells
Quaternary Ammonium Compounds / chemistry*
Transfection
Ultrasonic Waves*

Substances

Drug Carriers
Quaternary Ammonium Compounds
DNA