Nanoparticle-delivered suicide gene therapy effectively reduces ovarian tumor burden in mice

Yu Hung Huang, Gregory T. Zugates, Weidan Peng, David Holtz, Charles Dunton, Jordan J. Green, Naushad Hossain, Michael R. Chernick, Robert F. Padera, Robert Langer, Daniel G. Anderson, Janet A. Sawicki

Research output: Contribution to journalArticlepeer-review

Abstract

There is currently no effective therapy for patients with advanced ovarian cancer. To address the need for a more effective treatment for this deadly disease, we conducted preclinical tests in ovarian tumor-bearing mice to evaluate the therapeutic efficacy of using a cationic biodegradable poly(β-amino ester) polymer as a vector for nanoparticulate delivery of DNA encoding a diphtheria toxin suicide protein (DT-A). The promoter sequences of two genes that are highly active in ovarian tumor cells, MSLN and HE4, were used to target DT-A expression to tumor cells. Administration of DT-A nanoparticles directly to s.c. xenograft tumors and to the peritoneal cavity of mice bearing primary and metastatic ovarian tumors resulted in a significant reduction in tumor mass and a prolonged life span compared to control mice. Minimal nonspecific tissue and blood chemistry toxicity was observed following extended treatment with nanoparticles. DT-A nanoparticle therapy suppressed tumor growth more effectively than treatment with clinically relevant doses of cisplatin and paclitaxel. Our findings suggest that i.p. administration of polymeric nanoparticles to deliver DT-A encoding DNA, combined with transcriptional regulation to target gene expression to ovarian tumor cells, holds promise as an effective therapy for advanced-stage ovarian cancer.

Original languageEnglish (US)
Pages (from-to)6184-6191
Number of pages8
JournalCancer Research
Volume69
Issue number15
DOIs
StatePublished - Aug 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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