Surface charge-specific interactions between polymer nanoparticles and ABC transporters in Caco-2 cells

S. Bhattacharjee, E.J. van Opstal, G.M. Alink, A.T.M. Marcelis, H. Zuilhof, I.M.C.M. Rietjens

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)

Abstract

The surface charge-dependent transport of polymeric nanoparticles (PNPs) across Caco-2 monolayers grown on transwell culture systems as an in vitro model for intestinal transport was tested. The transport of well-characterized, monodisperse, and fluorescent tri-block copolymer nanoparticles (TCNPs/size ~45 nm) and polystyrene nanoparticles (PSNPs/size ~50 nm), with different surface charges (positive and negative), was quantified. The positive PNPs showed a higher intracellular uptake and flux across the Caco-2 monolayers than the negative PNPs. Multidrug resistance/P-glycoprotein (MDR1/P-gp), a specific ATP-binding cassette (ABC) transporter, was found to play a major role in the cellular efflux of positive PNPs, whereas the multidrug resistance protein 1 took part in the efflux of negative PNPs from Caco-2 cells. The positive PNPs also caused an increased cellular uptake and apical to basolateral transport of the carcinogen PhIP across the Caco-2 monolayer. The flavonoid quercetin, which is known to interact with ABC transporters, promoted the intracellular uptake of different PNPs and interfered with the normal distribution patterns of PNPs in the transwell system. These results indicate that PNPs display surface charge-specific interactions with ABC transporters and can even affect the bioavailability of toxic food-borne compounds (like pro-carcinogens).
Original languageEnglish
Article number1695
Number of pages14
JournalJournal of Nanoparticle Research : an Interdisciplinary Forum for Nanoscale Science and Technology
Volume15
DOIs
Publication statusPublished - 2013

Keywords

  • follicle-associated epithelium
  • in-vitro
  • drug-delivery
  • silicon nanoparticles
  • cellular uptake
  • stem-cells
  • monolayers
  • cytotoxicity
  • chitosan
  • trafficking

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