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

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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.
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Keywords: AS1411 aptamer; Nucleolin; PLGA; doxorubicin; internalization; targeted delivery

Document Type: Research Article

Publication date: 01 November 2018

This article was made available online on 27 July 2018 as a Fast Track article with title: "Cell Surface Nucleolin as a Promising Receptor for Effective AS1411 Aptamer-mediated Targeted Drug Delivery into Cancer Cells".

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  • The aim of Current Drug Delivery is to publish peer-reviewed articles, short communications, short and in-depth reviews in the rapidly developing field of drug delivery. Modern drug research aims to build in delivery properties of a drug at the design phase, however in many cases this ideal cannot be met and the development of delivery systems becomes as important as the development as the drugs themselves.

    The journal aims to cover the latest outstanding developments in drug and vaccine delivery employing physical, physico-chemical and chemical methods. The drugs include a wide range of bioactive compounds from simple pharmaceuticals to peptides, proteins, nucleotides, nucleosides and sugars. The journal will also report progress in the fields of transport routes and mechanisms including efflux proteins and multi-drug resistance.

    The journal is essential for all pharmaceutical scientists involved in drug design, development and delivery.
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