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

Jafar Mosafer1,2, Ahad Mokhtarzadeh3,4

  • 1Research Center of Advanced Technologies in Medicine, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.

Current Drug Delivery
|July 25, 2018
PubMed
Abstract

Insights

Targeted nanoparticles carrying chemotherapy drugs show enhanced uptake in cancer cells overexpressing nucleolin. This targeted drug delivery system utilizes the AS1411 aptamer to bind nucleolin receptors, improving therapeutic efficacy.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapeutics

Background:

  • Nucleolin is an abundant nuclear protein.
  • Overexpressed nucleolin on cell membranes of malignant and endothelial cells offers a target for drug delivery.

Purpose of the Study:

  • To investigate the targeting ability of anti-nucleolin AS1411 aptamer-targeted doxorubicin-encapsulated Poly lactic-co-glycolic acid (PLGA)-based nanoparticles (AS1411-NPs).
  • To compare the uptake of AS1411-NPs in high nucleolin-expressing C26 colon carcinoma and C6 glioma cell lines versus low nucleolin-expressing L929 cell line.

Main Methods:

  • Immunocytochemistry was used to assess cell surface nucleolin expression in C26, C6, and L929 cell lines.
  • Doxorubicin (Dox) was encapsulated into PLGA-based nanoparticles (NPs).
  • AS1411 aptamer was used to target the Dox-encapsulated PLGA-NPs.

Main Results:

  • C26 and C6 cell lines exhibited high nucleolin expression on their cytoplasmic membranes.
  • L929 cell line showed significantly lower nucleolin expression.
  • AS1411-NPs demonstrated more rapid internalization into C26 and C6 cells compared to L929 cells.

Conclusions:

  • AS1411-NPs bind to nucleolin receptors on the cell surface.
  • The receptor-ligand complex facilitates efficient cellular uptake via receptor-mediated endocytosis.
  • This targeted approach enhances drug delivery to high nucleolin-expressing cancer cells.
Keywords:
AS1411 aptamerNucleolinPLGAdoxorubicininternalizationtargeted delivery.

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