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

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1111-1118
Number of pages8
JournalBioconjugate Chemistry
Volume29
Issue number4
DOIs
StatePublished - Apr 18 2018

Bibliographical note

Funding Information:
This work was supported in part by the Children’s Cancer Research Fund (PMG). This work also utilized the University of Minnesota Masonic Cancer Center shared Flow Cytometry Facility, which is supported in part by NIH P30 CA77598. We thank members of the Gordon lab for helpful discussions.

Publisher Copyright:
© 2018 American Chemical Society.

Fingerprint

Dive into the research topics of 'SN-38 Conjugated Gold Nanoparticles Activated by Ewing Sarcoma Specific mRNAs Exhibit in Vitro and in Vivo Efficacy'. Together they form a unique fingerprint.

Cite this