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

  • Sourav Bhattacharjee
  • Edward J. van Opstal
  • Gerrit M. Alink
  • Antonius T. M. Marcelis
  • Han Zuilhof
  • Ivonne M. C. M. Rietjens
Research Paper


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).


Polymer nanoparticles Surface charge ABC transporters Caco-2 Transwell culture PhIP Quercetin Nanoparticle–food interactions 



The authors would like to thank the graduate school VLAG and Wageningen UR strategic research programme Bionanotechnology for funding.

Supplementary material

11051_2013_1695_MOESM1_ESM.pdf (196 kb)
Supplementary material 1 (PDF 196 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Sourav Bhattacharjee
    • 1
    • 2
  • Edward J. van Opstal
    • 2
  • Gerrit M. Alink
    • 2
  • Antonius T. M. Marcelis
    • 1
  • Han Zuilhof
    • 1
  • Ivonne M. C. M. Rietjens
    • 2
  1. 1.Laboratory of Organic ChemistryWageningen UniversityWageningenThe Netherlands
  2. 2.Division of ToxicologyWageningen UniversityWageningenThe Netherlands

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