SN-38 Conjugated Gold Nanoparticles Activated by Ewing Sarcoma Specific mRNAs Exhibit In Vitro and In Vivo Efficacy

Jordan A Naumann; John C Widen; Leslie A Jonart; Maryam Ebadi; Jian Tang; David J Gordon; Daniel A Harki; Peter M Gordon

doi:10.1021/acs.bioconjchem.7b00774

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SN-38 Conjugated Gold Nanoparticles Activated by Ewing Sarcoma Specific mRNAs Exhibit In Vitro and In Vivo Efficacy

Journal article

Peer reviewed

SN-38 Conjugated Gold Nanoparticles Activated by Ewing Sarcoma Specific mRNAs Exhibit In Vitro and In Vivo Efficacy

Jordan A Naumann, John C Widen, Leslie A Jonart, Maryam Ebadi, Jian Tang, David J Gordon, Daniel A Harki and Peter M Gordon

Bioconjugate chemistry, Vol.29(4), pp.1111-1118

04/18/2018

DOI: 10.1021/acs.bioconjchem.7b00774

PMCID: PMC7278042

PMID: 29412642

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https://www.ncbi.nlm.nih.gov/pmc/articles/7278042View

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Abstract

The limited delivery of chemotherapy agents to cancer cells and the nonspecific action of these agents are significant challenges in oncology. We have previously developed a customizable drug delivery and activation system in which a nucleic acid functionalized gold nanoparticle (Au-NP) delivers a drug that is selectively activated within a cancer cell by the presence of an mRNA unique to the cancer cell. The amount of drug released from sequestration to the Au-NP is determined by both the presence and the abundance of the cancer cell specific mRNA in a cell. We have now developed this technology for the potent, but difficult to deliver, topoisomerase I inhibitor SN-38. Herein, we demonstrate both the efficient delivery and selective release of SN-38 from gold nanoparticles in Ewing sarcoma cells with resulting efficacy in vitro and in vivo. These results provide further preclinical validation for this novel cancer therapy and may be extendable to other cancers that exhibit sensitivity to topoisomerase I inhibitors.

Gold - chemistry

Topoisomerase I Inhibitors - pharmacokinetics

Humans

Metal Nanoparticles - chemistry

Irinotecan - chemistry

Antineoplastic Agents - chemistry

Irinotecan - pharmacokinetics

RNA, Messenger - metabolism

Topoisomerase I Inhibitors - pharmacology

Cell Line, Tumor

Antineoplastic Agents - pharmacokinetics

Antineoplastic Agents - pharmacology

In Vitro Techniques

Sarcoma, Ewing - genetics

Irinotecan - pharmacology

Topoisomerase I Inhibitors - chemistry

Drug Screening Assays, Antitumor

Details

Title: Subtitle: SN-38 Conjugated Gold Nanoparticles Activated by Ewing Sarcoma Specific mRNAs Exhibit In Vitro and In Vivo Efficacy
Creators: Jordan A Naumann - University of Minnesota Masonic Cancer Center , Minneapolis , Minnesota 55455 , United States
John C Widen
Leslie A Jonart - University of Minnesota Masonic Cancer Center , Minneapolis , Minnesota 55455 , United States
Maryam Ebadi - University of Minnesota Masonic Cancer Center , Minneapolis , Minnesota 55455 , United States
Jian Tang
David J Gordon - Department of Pediatrics, Division of Pediatric Hematology/Oncology , University of Iowa , Iowa City , Iowa 52242 , United States
Daniel A Harki
Peter M Gordon - University of Minnesota Masonic Cancer Center , Minneapolis , Minnesota 55455 , United States
Resource Type: Journal article
Publication Details: Bioconjugate chemistry, Vol.29(4), pp.1111-1118
DOI: 10.1021/acs.bioconjchem.7b00774
PMID: 29412642
PMCID: PMC7278042
NLM abbreviation: Bioconjug Chem
ISSN: 1043-1802
eISSN: 1520-4812
Grant note: P30 CA086862 / NCI NIH HHS
Language: English
Date published: 04/18/2018
Academic Unit: Stead Family Department of Pediatrics; Hematology/Oncology
Record Identifier: 9984093507302771

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