| First Author | Huang YH | Year | 2009 |
| Journal | Cancer Res | Volume | 69 |
| Issue | 15 | Pages | 6184-91 |
| PubMed ID | 19643734 | Mgi Jnum | J:150935 |
| Mgi Id | MGI:3852565 | Doi | 10.1158/0008-5472.CAN-09-0061 |
| Citation | Huang YH, et al. (2009) Nanoparticle-delivered suicide gene therapy effectively reduces ovarian tumor burden in mice. Cancer Res 69(15):6184-91 |
| abstractText | 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(beta-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. |
