Drug conjugated nanoparticles activated by cancer cell specific mRNA

Nathan P. Gossai; Jordan A. Naumann; Nan-Sheng Li; Edward A. Zamora; David J. Gordon; Joseph A. Piccirilli; Peter M. Gordon

doi:10.18632/oncotarget.9430

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Research Papers:

Drug conjugated nanoparticles activated by cancer cell specific mRNA

Nathan P. Gossai, Jordan A. Naumann, Nan-Sheng Li, Edward A. Zamora, David J. Gordon, Joseph A. Piccirilli and Peter M. Gordon _

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Oncotarget. 2016; 7:38243-38256. https://doi.org/10.18632/oncotarget.9430

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Abstract

Nathan P. Gossai1,*, Jordan A. Naumann1,*, Nan-Sheng Li4, Edward A. Zamora1, David J. Gordon3, Joseph A. Piccirilli4,5, Peter M. Gordon1,2

1Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Minnesota, Minneapolis, MN, USA

2University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA

3Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Iowa, Iowa City, IA, USA

4Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA

5Department of Chemistry, University of Chicago, Chicago, IL, USA

*These authors have contributed equally to this work

Correspondence to:

Peter M. Gordon, email: [email protected]

Keywords: gold nanoparticles, drug delivery, leukemia, molecularly targeted therapy, anti-sense

Received: February 08, 2016 Accepted: May 01, 2016 Published: May 18, 2016

ABSTRACT

We describe a customizable approach to cancer therapy in which a gold nanoparticle (Au-NP) delivers a drug that is selectively activated within the cancer cell by the presence of an mRNA unique to the cancer cell. Fundamental to this approach is the observation that the amount of drug released from the Au-NP is proportional to both the presence and abundance of the cancer cell specific mRNA in a cell. As proof-of-principle, we demonstrate both the efficient delivery and selective release of the multi-kinase inhibitor dasatinib from Au-NPs in leukemia cells with resulting efficacy in vitro and in vivo. Furthermore, these Au-NPs reduce toxicity against hematopoietic stem cells and T-cells. This approach has the potential to improve the therapeutic efficacy of a drug and minimize toxicity while being highly customizable with respect to both the cancer cell specific mRNAs targeted and drugs activated.

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PII: 9430

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Research Papers:

Drug conjugated nanoparticles activated by cancer cell specific mRNA

Abstract