RRC ID 67515
Author Arai M, Komori H, Fujita D, Tamai I.
Title Uptake Pathway of Apple-derived Nanoparticle by Intestinal Cells to Deliver its Cargo.
Journal Pharm Res
Abstract PURPOSE:Food-derived nanoparticles exert cytoprotective effects on intestinal cells by delivering their cargo, which includes macromolecules such as microRNAs and proteins, as well as low-molecular weight compounds. We previously reported that apple-derived nanoparticles (APNPs) downregulate the expression of human intestinal transporter OATP2B1/SLCO2B1 mRNA. To verify the involvement of the cargo of APNPs in affecting the expression of transporters, we characterized the uptake mechanism of APNPs in intestinal cells.
METHODS:The uptake of fluorescent PKH26-labeled APNPs (PKH-APNPs) into Caco-2, LS180, and HT-29MTX cells was evaluated by confocal microscopy and flow cytometry.
RESULTS:The uptake of PKH-APNPs was prevented in the presence of clathrin-dependent endocytosis inhibitors, chlorpromazine and Pitstop2. Furthermore, PKH-APNPs were incorporated by the HT29-MTX cells, despite the disturbance of the mucus layer. Additionally, the decrease in SLCO2B1 mRNA by APNPs was reversed by Pitstop 2 in Caco-2 cells, indicating that APNPs decrease SLCO2B1 by being incorporated via clathrin-dependent endocytosis.
CONCLUSIONS:We demonstrated that clathrin-dependent endocytosis was mainly involved in the uptake of APNPs by intestinal cells, and that the cargo in the APNPs downregulate the mRNA expression of SLCO2B1. Therefore, APNPs could be a useful tool to deliver large molecules such as microRNAs to intestinal cells.
Volume 38(3)
Pages 523-530
Published 2021-3-1
DOI 10.1007/s11095-021-03018-8
PII 10.1007/s11095-021-03018-8
PMID 33723795
MeSH Biological Transport Caco-2 Cells Clathrin / metabolism Endocytosis Fluorescent Dyes / chemistry Gene Expression Regulation / drug effects HT29 Cells Humans Intestines / cytology Intestines / pathology* Malus / chemistry* Nanoparticles / chemistry* Nanoparticles / metabolism* Optical Imaging Organic Anion Transporters / genetics Organic Anion Transporters / metabolism RNA, Messenger / metabolism Signal Transduction Tissue Distribution
IF 3.242
Human and Animal Cells CACO-2(RCB0988)