Apple-Derived Nanoparticles Modulate Expression of Organic-Anion-Transporting Polypeptide (OATP) 2B1 in Caco-2 Cells

Mol Pharm. 2018 Dec 3;15(12):5772-5780. doi: 10.1021/acs.molpharmaceut.8b00921. Epub 2018 Nov 5.


Interaction of foods with intestinal transporters has generally been ascribed to small molecules, but recently, edible-plant-derived nanoparticles (NPs) have been suggested to affect intestinal function. Here, we examined the effects of NPs contained in edible fruits on intestinal transporters. Apple-derived NPs (APNPs) were isolated by ultracentrifugation and characterized by measurement of particle size distribution and electron microscopy. Human epithelial colorectal adenocarcinoma (Caco-2) cells internalized fluorescently labeled APNPs, suggesting that fruit-derived NPs would be internalized into intestinal epithelial cells in vivo. We found that the mRNA expression levels of several transporters, including organic-anion-transporting polypeptide (OATP) 2B1, were changed in APNP-treated Caco-2 cells. The protein expression and activity of OATP2B1 were also decreased by APNP exposure, as determined by Western blotting and measurements of [3H]estrone-3-sulfate uptake by Caco-2 cells, respectively. These actions required intact APNPs, because sonication or boiling abrogated the effects. Since the content of apple-derived small molecules in APNPs was negligible, the observed decrease of OATP2B1 expression appears to be mediated by large molecules in the APNPs. We further found that the 3'-untranslated region of the OATP2B1 gene was required for the response to APNPs, suggesting that microRNA in the APNPs might be involved. These results propose a novel mechanism, in which large molecules such as microRNA in food could affect intestinal transporters through food-derived NPs, which also demonstrates that food-derived NPs should be useful for delivery of biologically active large molecules to intestinal tissues.

Keywords: drug−food interaction; edible nanoparticle; extracellular vesicle; fruit; intestine; microRNA; transporter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacokinetics*
  • Fruit / chemistry*
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism
  • Malus / chemistry*
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry
  • Organic Anion Transporters / metabolism*
  • Plants, Edible / chemistry*


  • Drug Carriers
  • Organic Anion Transporters
  • SLCO2B1 protein, human