Induction of oxidative stress, lysosome activation and autophagy by nanoparticles in human brain-derived endothelial cells.
Different types of NPs (nanoparticles) are currently under development for diagnostic and therapeutic applications in the biomedical field, yet our knowledge about their possible effects and fate in living cells is still limited. In the present study, we examined the cellular response of human brain-derived endothelial cells to NPs of different size and structure: uncoated and oleic acid-coated iron oxide NPs (8-9 nm core), fluorescent 25 and 50 nm silica NPs, TiO2 NPs (21 nm mean core diameter) and PLGA [poly(lactic-co-glycolic acid)]-PEO [poly(ethylene oxide)] polymeric NPs (150 nm). We evaluated their uptake by the cells, and their localization, generation of oxidative stress and DNA-damaging effects in exposed cells. We show that NPs are internalized by human brain-derived endothelial cells; however, the extent of their intracellular uptake is dependent on the characteristics of the NPs. After their uptake by human brain-derived endothelial cells NPs are transported into the lysosomes of these cells, where they enhance the activation of lysosomal proteases. In brain-derived endothelial cells, NPs induce the production of an oxidative stress after exposure to iron oxide and TiO2 NPs, which is correlated with an increase in DNA strand breaks and defensive mechanisms that ultimately induce an autophagy process in the cells.
University of Lausanne, Rue du Bugnon 25, CH-1011 Lausanne, Switzerland.
Blanka
B
Halamoda Kenzaoui
Catherine
C
Chapuis Bernasconi
Seher
S
Guney-Ayra
Lucienne
L
Juillerat-Jeanneret
D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D019344:Lactic Acid / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism; D053758:Nanoparticles / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011100:Polyglycolic Acid / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000009:adverse effects / Q000494:pharmacology*; D014025:Titanium / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D011108:Polymers; C009495:titanium dioxide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004247:DNA; D014025:Titanium