Drug conjugated nanoparticles activated by cancer cell specific mRNA

Abstract

// Nathan P. Gossai 1, * , Jordan A. Naumann 1, * , Nan-Sheng Li 4 , Edward A. Zamora 1 , David J. Gordon 3 , Joseph A. Piccirilli 4, 5 , Peter M. Gordon 1, 2 1 Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Minnesota, Minneapolis, MN, USA 2 University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA 3 Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Iowa, Iowa City, IA, USA 4 Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA 5 Department of Chemistry, University of Chicago, Chicago, IL, USA * These authors have contributed equally to this work Correspondence to: Peter M. Gordon, email: gord0047@umn.edu 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.