Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 64, Issue 3, Pages 356-364Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-007-6390-x
Keywords
rat brain endothelial cells; PEGylated nanoparticles; poly(alkylcyanoacrylate); clathrin-coated pits; low-density lipoprotein receptor-mediated endocytosis; apolipoprotein E
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Poly(methoxypolyethyleneglycol cyanoacrylate-co-hexadecylcyanoacrylate) (PEG-PHDCA) nanoparticles have demonstrated their capacity to diffuse through the blood-brain barrier after intravenous administration. However, the mechanism of transport of these nanoparticles into brain has not yet been clearly elucidated. The development of a model of rat brain endothelial cells (RBEC) in culture has allowed investigations into this mechanism. A study of the intracellular trafficking of nanoparticles by cell fractionation and confocal microscopy showed that nanoparticles are internalized by the endocytic pathway. Inhibition of the caveolae-mediated pathway by preincubation with filipin and nystatin did not modify the cellular uptake of the nanoparticles. In contrast, chlorpromazine and NaN3 pretreatment, which interferes with clathrin and energy-dependent endocytosis, caused a significant decrease of nanoparticle internalization. Furthermore, cellular uptake experiments with nanoparticles preincubated with apolipoprotein E and blocking of low-density lipoprotein receptors (LDLR) clearly suggested that the LDLR-mediated pathway was involved in the endocytosis of PEG-PHDCA nanoparticles by RBEC.
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