Cell Surface Nucleolin as a Promising Receptor for Effective AS1411 Aptamer-Mediated Targeted Drug Delivery into Cancer Cells.

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.