Hybrid vesicles as intracellular reactive oxygen species and nitric oxide generators

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DOI

  • Yan Zhang
  • Noga Gal
  • Fabian Itel
  • ,
  • Isabella N. Westensee
  • Edit Brodszkij
  • Daniel Mayer, Univ Hosp Ulm, Ulm University, Inst Med Microbiol & Infect Control
  • ,
  • Steffen Stenger, Univ Hosp Ulm, Ulm University, Inst Med Microbiol & Infect Control
  • ,
  • Miquel Castellote-Borrell, Aarhus Univ, Aarhus University, Interdisciplinary Nanosci Ctr iNANO
  • ,
  • Thomas Boesen
  • Seyed R. Tabaei, Chalmers Univ Technol, Chalmers University of Technology, Dept Phys
  • ,
  • Fredrik Hook, Chalmers Univ Technol, Chalmers University of Technology, Dept Phys
  • ,
  • Brigitte Stadler

Artificial organelles are envisioned as nanosized assemblies with intracellular biocatalytic activity to provide the host cells with non-native or missing/lost function. Hybrid vesicles loaded with glucose oxidase (NRGOx) or beta-galactosidase (NR beta-Gal) and equipped with lysosomal escape ability are assembled using phospholipids and the block copolymer poly(cholesteryl methacrylate)-block-poly(2-(dimethylamino)ethyl methacrylate). The co-localization of the building blocks and the catalytic activity of NRGOx and NR beta-Gal are illustrated. The intracellular activity of the nanoreactors in RAW 264.7 macrophages is confirmed by an enhanced reduction in viability for cells pre-incubated with NRGOx in the presence of glucose due to the generation of cytotoxic hydrogen peroxide compared to the controls. In addition, RAW 264.7 macrophages and primary human macrophages equipped with NR beta-Gal are able to intracellularly convert beta-Gal-NONOate into nitric oxide. The successful use of these hybrid vesicles to equip host macrophages with additional catalytic activity diversifies the available toolbox of nanocarriers with envisioned application in cell mimicry.

OriginalsprogEngelsk
TidsskriftNanoscale
Vol/bind11
Nummer24
Sider (fra-til)11530-11541
Antal sider12
ISSN2040-3364
DOI
StatusUdgivet - jun. 2019

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