論文

筆頭著者 国際誌
2017年12月27日

Polyplex Micelles with Phenylboronate/Gluconamide Cross-Linking in the Core Exerting Promoted Gene Transfection through Spatiotemporal Responsivity to Intracellular pH and ATP Concentration.

Journal of the American Chemical Society
  • Naoto Yoshinaga
  • ,
  • Takehiko Ishii
  • ,
  • Mitsuru Naito
  • ,
  • Taisuke Endo
  • ,
  • Satoshi Uchida
  • ,
  • Horacio Cabral
  • ,
  • Kensuke Osada
  • ,
  • Kazunori Kataoka

139
51
開始ページ
18567
終了ページ
18575
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1021/jacs.7b08816

Polyplexes as gene delivery carriers require integrated functionalities to modulate intracellular trafficking for efficient gene transfection. Herein, we developed plasmid DNA (pDNA)-loaded polyplex micelles (PMs) from poly(ethylene glycol)-based block catiomers derivatized with 4-carboxy-3-fluorophenylboronic acid (FPBA) and d-gluconamide to form pH- and ATP-responsive cross-linking in the core. These PMs exhibited robustness in the extracellular milieu and smooth endosomal escape after cellular uptake, and they facilitated pDNA decondensation triggered by increased ATP concentration inside of the cell. Laser confocal microscopic observation revealed that FPBA installation enhanced the endosomal escapability of the PMs; presumably, this effect resulted from the facilitated endo-/lysosomal membrane disruption triggered by the released block catiomers with hydrophobic FPBA moieties in the side chain from the PM at lower pH condition of endo-/lysosomes. Furthermore, the profile of intracellular pDNA decondensation from the PMs was monitored using Förster resonance energy transfer measurement by flow cytometry; these observations confirmed that PMs optimized for ATP-responsivity exerted effective intracellular decondensation of loaded pDNA to attain promoted gene transfection.

リンク情報
DOI
https://doi.org/10.1021/jacs.7b08816
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29188718
ID情報
  • DOI : 10.1021/jacs.7b08816
  • PubMed ID : 29188718

エクスポート
BibTeX RIS