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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Drug conjugated nanoparticles activated by cancer cell specific mRNA

Journal article

Open access

Peer reviewed

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

Oncotarget, Vol.7(25), pp.38243-38256

06/21/2016

DOI: 10.18632/oncotarget.9430

PMCID: PMC5122386

PMID: 27203672

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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.

Neoplasms - metabolism

Gold - administration & dosage

Humans

Metal Nanoparticles - chemistry

Drug Carriers - administration & dosage

Gold - metabolism

Dasatinib - pharmacokinetics

Antineoplastic Agents - administration & dosage

RNA, Messenger - metabolism

Neoplasms - drug therapy

Xenograft Model Antitumor Assays

Animals

Dasatinib - administration & dosage

Metal Nanoparticles - administration & dosage

Neoplasms - genetics

HEK293 Cells

K562 Cells

Cell Line, Tumor

Antineoplastic Agents - pharmacokinetics

Drug Carriers - pharmacokinetics

Mice

Neoplasms - pathology

3T3 Cells

Details

Title: Subtitle: Drug conjugated nanoparticles activated by cancer cell specific mRNA
Creators: Nathan P Gossai - Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Minnesota, Minneapolis, MN, USA
Jordan A Naumann - Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Minnesota, Minneapolis, MN, USA
Nan-Sheng Li - Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA
Edward A Zamora - Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Minnesota, Minneapolis, MN, USA
David J Gordon - Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Iowa, Iowa City, IA, USA
Joseph A Piccirilli - Department of Chemistry, University of Chicago, Chicago, IL, USA
Peter M Gordon - University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA
Resource Type: Journal article
Publication Details: Oncotarget, Vol.7(25), pp.38243-38256
DOI: 10.18632/oncotarget.9430
PMID: 27203672
PMCID: PMC5122386
NLM abbreviation: Oncotarget
ISSN: 1949-2553
eISSN: 1949-2553
Grant note: P30 CA077598 / NCI NIH HHS K08 CA154782 / NCI NIH HHS
Language: English
Date published: 06/21/2016
Academic Unit: Stead Family Department of Pediatrics; Hematology/Oncology
Record Identifier: 9984093366602771

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