Developing lipid nanoparticle-based siRNA therapeutics for hepatocellular carcinoma using an integrated approach
| Autor: | Carol K. Wada, Prasad A. Dande, Xiaoyu Lin, William M. Kohlbrenner, Lu Tian, Stephen W. Fesik, Robert D. Hubbard, Xiaoli Huang, Denise Wilcox, Aparna Sarthy, Xiaobin Zhao, Yu Shen, Leiming Li, Todd M. Hansen, Rongqi Wang |
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| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Carcinoma Hepatocellular Liver toxicity Mice SCID Pharmacology Biology Mice Drug Delivery Systems Liver Neoplasms Experimental Cell Line Tumor medicine Animals Humans RNA Small Interfering Gene knockdown Liver Neoplasms Genetic Therapy Hep G2 Cells Integrated approach medicine.disease Oncology Hepatocellular carcinoma Cancer research Nanoparticles Female Delivery system |
| Zdroj: | Molecular cancer therapeutics. 12(11) |
| ISSN: | 1538-8514 |
| Popis: | Successful siRNA therapeutics requires the optimal integration of multiple components, including an efficient delivery system, a disease indication that is appropriate for siRNA-based therapy, and a potent and nontoxic siRNA against a robust therapeutic target. Although all currently available delivery systems have limitations, it is important to recognize that a careful selection of the disease indication, therapeutic target, and siRNA molecule could partially compensate for deficiencies associated with the delivery system and makes it possible to advance a therapeutic siRNA regimen. In this study, we present the development of siRNA therapeutics for hepatocellular carcinoma using an integrated approach, including the development of an efficient lipid nanoparticle delivery system, the identification of a robust therapeutic target that does not trigger liver toxicity upon target knockdown, and the selection of potent and nonimmunogenic siRNA molecules against the target. The resulting siRNA-containing lipid nanoparticles produced significant antitumor efficacy in orthotopic hepatocellular carcinoma models, and, thus, represent a promising starting point for the development of siRNA therapeutics for hepatocellular carcinoma. Mol Cancer Ther; 12(11); 2308–18. ©2013 AACR. |
| Databáze: | OpenAIRE |
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