TY - JOUR

T1 - Hybrid vesicles as intracellular reactive oxygen species and nitric oxide generators

AU - Zhang, Yan

AU - Gal, Noga

AU - Itel, Fabian

AU - Westensee, Isabella N.

AU - Brodszkij, Edit

AU - Mayer, Daniel

AU - Stenger, Steffen

AU - Castellote-Borrell, Miquel

AU - Boesen, Thomas

AU - Tabaei, Seyed R.

AU - Hook, Fredrik

AU - Stadler, Brigitte

PY - 2019/6

Y1 - 2019/6

N2 - 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.

AB - 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.

KW - NANOREACTORS

KW - DELIVERY

KW - ENZYMES

KW - NANOPARTICLES

KW - ORGANELLES

KW - RELEASE

U2 - 10.1039/c9nr02584g

DO - 10.1039/c9nr02584g

M3 - Journal article

C2 - 31150038

VL - 11

SP - 11530

EP - 11541

JO - Nanoscale

JF - Nanoscale

SN - 2040-3364

IS - 24

ER -