Uptake Pathway of Apple-derived Nanoparticle by Intestinal Cells to Deliver its Cargo

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 exp...

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Bibliographic Details
Published in:Pharmaceutical research 2021-03, Vol.38 (3), p.523-530
Main Authors: Arai, Mayumi, Komori, Hisakazu, Fujita, Daichi, Tamai, Ikumi
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Chlorpromazine
Clathrin
Confocal microscopy
Endocytosis
Flow cytometry
Gene expression
Intestine
Macromolecules
Medical Law
MicroRNA
MicroRNAs
miRNA
Molecular weight
Nanoparticles
Penicillin G
Pharmacology/Toxicology
Pharmacy
Research Paper
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Summary: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.
ISSN:0724-8741
1573-904X
DOI:10.1007/s11095-021-03018-8