Oncotarget

Research Papers:

AS1411-conjugated gold nanospheres and their potential for breast cancer therapy

Mohammad T. Malik _, Martin G. O’Toole, Lavona K. Casson, Shelia D. Thomas, Gina T. Bardi, Elsa Merit Reyes-Reyes, Chin K. Ng, Kyung A. Kang and Paula J. Bates

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Oncotarget. 2015; 6:22270-22281. https://doi.org/10.18632/oncotarget.4207

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Abstract

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

Correspondence to:

Mohammad T. Malik, e-mail: tariq.malik@louisville.edu

Paula J. Bates, e-mail: paula.bates@louisville.edu

Keywords: targeted therapy, nanomedicine, triple negative breast cancer, G-quadruplex, nanoparticles

Received: May 11, 2015     Accepted: May 22, 2015     Published: June 03, 2015

ABSTRACT

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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