Title:Cell Surface Nucleolin as a Promising Receptor for Effective AS1411 Aptamer-Mediated Targeted Drug Delivery into Cancer Cells
Volume: 15
Issue: 9
Author(s): Jafar Mosafer*Ahad Mokhtarzadeh
Affiliation:
- Research Center of Advanced Technologies in Medicine, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh,Iran
Keywords:
Nucleolin, AS1411 aptamer, targeted delivery, internalization, PLGA, doxorubicin.
Abstract: Background: One of the major abundant proteins in the nucleous is nucleolin that
overexpressed on the cytoplasmic membrane of malignant and endothelial cells and makes it as a
promising condidate for targeted drug delivery.
Objectives: In this study, doxorubicin (Dox) as a chemotherapy drug was entrapped into the Poly lacticco-
glycolic acid (PLGA)-based nanoparticles (NPs). Then, the targeting ability of anti nucleolin
AS1411 aptamer-targeted Dox-encapsulated PLGA-based NPs (AS1411-NPs) was investigated in high
nucleolin-expressing C26 colon carcinoma and rat C6 glioma cell lines compared with low nucleolinexpressing
mouse L929 cell line.
Methods: We recently first assessed the existence of cell surface nucleolin of these three different cell
lines by immunocytochemistry method. We found that a large amount of nucleolin was localized in the
cytoplasmic membrane of C26 and C6 cell lines, with a very smaller amount on the surface of L929 cell
line.
Results: As a result, more rapidly internalization of AS1411-NPs into the C26 and C6 cells compared
with L929 cells was verified.
Conclusion: We think that AS1411-NPs, as a ligand, first bind to nucleolin, as a receptor, and then the
receptor-ligand complex is more efficiently incorporated into the high nucleolin-expressing cell lines
through receptor-mediated endocytosis pathway.