AS1411-conjugated gold nanospheres and their potential for breast cancer therapy
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Mohammad T. Malik1,5, Martin G. O’Toole2, Lavona K. Casson1,5, Shelia D. Thomas1,5, Gina T. Bardi1,5, Elsa Merit Reyes-Reyes1,5, Chin K. Ng3, Kyung A. Kang4, Paula J. Bates1,5
1Departments of Medicine, University of Louisville, Louisville, Kentucky, USA
2Departments of Bioengineering, University of Louisville, Louisville, Kentucky, USA
3Departments of Radiology, University of Louisville, Louisville, Kentucky, USA
4Departments of Chemical Engineering, University of Louisville, Louisville, Kentucky, USA
5Departments of the Molecular Targets Group of the James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA
Mohammad T. Malik, e-mail: firstname.lastname@example.org
Paula J. Bates, e-mail: email@example.com
Keywords: targeted therapy, nanomedicine, triple negative breast cancer, G-quadruplex, nanoparticles
Received: May 11, 2015 Accepted: May 22, 2015 Published: June 03, 2015
AS1411 is a quadruplex-forming DNA oligonucleotide that functions as an aptamer to target nucleolin, a protein present on the surface of cancer cells. Clinical trials of AS1411 have indicated it is well tolerated with evidence of therapeutic activity, but improved pharmacology and potency may be required for optimal efficacy. In this report, we describe how conjugating AS1411 to 5 nm gold nanospheres influences its activities in vitro and in vivo. We find that the AS1411-linked gold nanospheres (AS1411-GNS) are stable in aqueous and serum-containing solutions. Compared to unconjugated AS1411 or GNS linked to control oligonucleotides, AS1411-GNS have superior cellular uptake and markedly increased antiproliferative/cytotoxic effects. Similar to AS1411, AS1411-GNS show selectivity for cancer cells compared to non-malignant cells. In a mouse model of breast cancer, systemic administration of AS1411-GNS could completely inhibit tumor growth with no signs of toxicity. These results suggest AS1411-GNS are promising candidates for clinical translation.
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