Hybrid vesicles as intracellular reactive oxygen species and nitric oxide generators

Yan Zhang, Noga Gal, Fabian Itel, Isabella N. Westensee, Edit Brodszkij, Daniel Mayer, Steffen Stenger, Miquel Castellote-Borrell, Thomas Boesen, Seyed R. Tabaei, Fredrik Hook, Brigitte Stadler*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

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 (NR GOx) or β-galactosidase (NR β-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 NR GOx and NR β-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 NR GOx 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 β-Gal are able to intracellularly convert β-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.

Original languageEnglish
JournalNanoscale
Volume11
Issue24
Pages (from-to)11530-11541
Number of pages12
ISSN2040-3364
DOIs
Publication statusPublished - Jun 2019

Keywords

  • NANOREACTORS
  • DELIVERY
  • ENZYMES
  • NANOPARTICLES
  • ORGANELLES
  • RELEASE

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