Targeted nanomedicine for suppression of CD44 and simultaneous cell death induction in ovarian cancer: an optimal delivery of siRNA and anticancer drug.
Targeted nanomedicine for suppression of CD44 and simultaneous cell death induction in ovarian cancer: an optimal delivery of siRNA and anticancer drug.
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DOI：
10.1158/1078-0432.ccr-13-1536
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发表时间：
2013-11-15
期刊：
影响因子：
--
通讯作者：
Minko T
中科院分区：
文献类型：
--
作者：
Shah V;Taratula O;Garbuzenko OB;Taratula OR;Rodriguez-Rodriguez L;Minko T
The proposed project is aimed at enhancing the efficiency of epithelial ovarian cancer treatment and reducing adverse side effects of chemotherapy using nanotechnology. Overexpression of the CD44 membrane receptor results in tumor initiation, growth, tumor stem cells specific behavior, development of drug resistance, and metastases. We hypothesize that a developed cancer targeted delivery system which combines CD44 siRNA with paclitaxel would successfully deliver its payload inside cancer cells, effectively induce cell death, and prevent metastases. We synthesized, characterized, and tested a nanoscale-based drug delivery system containing a modified Polypropylenimine (PPI) dendrimer as a carrier; anticancer drug paclitaxel as a cell death inducer; a synthetic analog of luteinizing hormone-releasing hormone (LHRH) peptide as a tumor targeting moiety, and siRNA targeted to CD44 mRNA. The proposed NDDS was tested in vitro and in vivo using metastatic ovarian cancer cells isolated from patients with malignant ascites. We found that in contrast to cells isolated from primary tumors, CD44 was highly overexpressed in metastatic cancer cells. Treatment with the proposed tumor-targeted nanoscale-based nucleic acid and drug delivery system led to the suppression of CD44 mRNA and protein, efficient induction of cell death, effective tumor shrinkage, and prevention of adverse side effects on healthy organs. We show a high therapeutic potential for combinatorial treatment of ovarian carcinoma with a novel drug delivery system that effectively transports siRNA targeting to CD44 mRNA simultaneously with cytotoxic agents.
