Nanoparticle-delivered suicide gene therapy effectively reduces ovarian tumor burden in mice.
Nanoparticle-delivered suicide gene therapy effectively reduces ovarian tumor burden in mice.
复制标题
DOI：
10.1158/0008-5472.can-09-0061
复制
发表时间：
2009-08-01
期刊：
影响因子：
11.2
通讯作者：
Sawicki JA
中科院分区：
文献类型：
--
作者：
Huang YH;Zugates GT;Peng W;Holtz D;Dunton C;Green JJ;Hossain N;Chernick MR;Padera RF Jr;Langer R;Anderson DG;Sawicki JA
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 pre-clinical 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 gene (DT-A). The promoter sequences of two genes that are highly active in ovarian tumor cells, mesothelin and HE4, were used to target DT-A expression to tumor cells. Administration of DT-A nanoparticles directly to subcutaneous 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 lifespan compared to control mice. Minimal non-specific 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 intraperitoneal 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.
