Low-density lipoprotein receptor-mediated endocytosis of PEGylated nanoparticles in rat brain endothelial cells (original) (raw)

Abstract.

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 PEGPHDCA nanoparticles by RBEC.

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Authors and Affiliations

1. Laboratory of Biopharmacy and Pharmaceutical Technology, Faculty of Pharmacy, UMR 8612, IFR 141, CNRS, University of Paris-Sud 11, 5, rue J. B. Clément, 92296, Châtenay-Malabry, France
   H. Ryoung Kim, K. Andrieux, M. Appel, H. Chacun & P. Couvreur
2. UPRES 2706, IFR 141, University of Paris-Sud, 92296, Châtenay-Malabry, France
   S. Gil
3. Unit of Imagery, IFR 141, University of Paris-Sud, 92296, Châtenay-Malabry, France
   V. Nicolas
4. IFR 141, CNRS, UMR8076, 92296, Châtenay-Malabry, France
   D. Desmaële
5. University of Paris-Sud, 92296, Châtenay-Malabry, France
   D. Desmaële
6. Department of Radiolabeled Molecules, CEA/Saclay, 91191, Gif sur Yvette, France
   F. Taran & D. Georgin

Authors

1. H. Ryoung Kim
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2. S. Gil
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3. K. Andrieux
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4. V. Nicolas
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5. M. Appel
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6. H. Chacun
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7. D. Desmaële
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8. F. Taran
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9. D. Georgin
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10. P. Couvreur
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Corresponding author

Correspondence toK. Andrieux.

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Received 1 September 2006; received after revision 4 December 2006; accepted 18 December 2006

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Kim, H.R., Gil, S., Andrieux, K. et al. Low-density lipoprotein receptor-mediated endocytosis of PEGylated nanoparticles in rat brain endothelial cells.Cell. Mol. Life Sci. 64, 356–364 (2007). https://doi.org/10.1007/s00018-007-6390-x

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• Published: 26 January 2007
• Issue Date: February 2007
• DOI: https://doi.org/10.1007/s00018-007-6390-x

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