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The systemic delivery of siRNAs by a cell penetrating peptide, low molecular weight protamine
- The systemic delivery of siRNAs by a cell penetrating peptide, low molecular weight protamine
- Choi Y.-S.; Lee J.Y.; Suh J.S.; Kwon Y.-M.; Lee S.-J.; Chung J.-K.; Lee D.-S.; Yang V.C.; Chung C.-P.; Park Y.-J.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Biomaterials vol. 31, no. 6, pp. 1429 - 1443
- SCI; SCIE; SCOPUS
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- Small interfering RNAs (siRNAs), used for specific down-regulation of targeted genes, have garnered considerable interest as an attractive new class of drugs for broad clinical applications. The polyanionic charges carried by these siRNAs, however, restrain cellular uptake and consequently limit effects on gene regulation. Herein the authors describe a peptide/siRNA complex containing the cell penetrating peptide derived from natural protamine, termed low molecular weight protamine (LMWP), for the treatment of cancer. Fluorescently-tagged siRNAs were localized with the peptide in the cytoplasm shortly after incubation of LMWP/siRNA complex with carcinoma cells. The increased cell uptake of siRNA that was achieved using the LMWP resulted in significant down-regulation of model protein luciferase as well as therapeutic cancer target, vascular endothelial growth factor (VEGF) expression. In vivo studies with tumor-bearing mice further demonstrated that the peptide could carry and localize siRNA inside tumors and inhibit the expression of VEGF through systemic application of the peptide complex, thereby suppressing tumor growth. In addition, no detectable increase in the serum level of inflammatory cytokines including interferon (IFN)-α and interleukin (IL)-12 was observed under the LMWP/siRNA complex treatment, indicating systemic delivery of LMWP/siRNA did not exert measurable immunostimulatory effect. The LMWP-based systemic delivery method could be a reliable and safe approach to maximize effectiveness of therapeutic siRNA for treatment of cancer and other diseases. © 2009 Elsevier Ltd. All rights reserved.
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