Aptamer Functionalized Gold Nanoparticles as a Molecular Nanoconstruct to Specifically Target Cancer Cells

Introduction: Advances in nanotechnology have led to development of modern avenues in biomedical research; including application of different nanoparticles to deliver exogenous therapeutics to cancer cells. Meanwhile, externally applied nucleic acids provide a promising platform for therapeutics by targeting various cellular signaling pathways involved in cancer and genetic disorders; however, maintaining optimum stability during delivery has limited their application. To this aim, a number of biological and synthetic vectors were failed due to their low storage stability, lack of targeting efficacy, and limited in vivo tracking. In the last decades, gold nanoparticles with their unique properties were shown to be highly efficient inorganic vectors to overcome these obstacles. Methods: In this study an Apt-AuNP complex was prepared using 15nm gold nanoparticles as a delivery vehicle and AS1411 aptamer to target nucleolin, a protein present on the surface of cancer cells. Amine-functionalized aptamers were conjugated with AuNPs chemically attached to polyA tails containing thiol groups in one end and carboxyl groups in the other. Results: UV-visible spectra of the compounds showed a peak in both 260nm and 525nm indicating formation of Apt-AuNP complexes which was subsequently confirmed by gel retardation assay and Atomic Forced Microscopy. Monitoring cellular uptake of FAM-labelled aptamers demonstrated the efficient delivery of conjugates to MCF-7 breast cancer cells. Conclusion: Application of such polyA-based AuNPs not only avoids the use of thiolated oligonucleotides and subsequent thiol-containing displacing reagents, but also allows convenient conjugation of different amine containing extra-cellular biomolecules to gold nanoparticles for bioanalytical purposes.

Keywords:

Aptamer , Gold nanoparticles , Cancer , Targeted delivery