Sustained small interfering RNA delivery by mesoporous silicon particles
| Autor: | Anil K. Sood, Biana Godin, Takemi Tanaka, Mian M.K. Shahzad, Lingegowda S. Mangala, Koji Matsuo, Gabriel Lopez-Berestein, Jianhua Gu, Jean R. Fakhoury, Pablo E. Vivas-Mejia, Hee Dong Han, René Nieves-Alicea, Aman P. Mann, Edna M. Mora, Rohan Bhavane, Rebecca L. Stone, Alpa M. Nick, Ciro Chiappini, Xuewu Liu, Chunhua Lu, Mauro Ferrari |
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| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
Small interfering RNA Silicon Angiogenesis Mice Nude Biology Proinflammatory cytokine Mice RNA interference In vivo Cell Line Tumor medicine Gene silencing Animals Humans Gene Silencing RNA Small Interfering Ovarian Neoplasms Receptor EphA2 RNA Genetic Therapy medicine.disease Molecular biology Xenograft Model Antitumor Assays Oncology Liposomes Cancer research Phosphatidylcholines Nanoparticles Female Ovarian cancer |
| Zdroj: | Tanaka, T, Mangala, L S, Vivas-Mejia, P E, Nieves-Alicea, R, Mann, A P, Mora, E, Han, H-D, Shahzad, M M K, Liu, X, Bhavane, R, Gu, J, Fakhoury, J R, Chiappini, C, Lu, C, Matsuo, K, Godin, B, Stone, R L, Nick, A M, Lopez-Berestein, G, Sood, A K & Ferrari, M 2010, ' Sustained small interfering RNA delivery by mesoporous silicon particles ', Cancer Research, vol. 70, no. 9, pp. 3687-3696 . https://doi.org/10.1158/0008-5472.CAN-09-3931 |
| ISSN: | 1538-7445 |
| DOI: | 10.1158/0008-5472.CAN-09-3931 |
| Popis: | RNA interference (RNAi) is a powerful approach for silencing genes associated with a variety of pathologic conditions; however, in vivo RNAi delivery has remained a major challenge due to lack of safe, efficient, and sustained systemic delivery. Here, we report on a novel approach to overcome these limitations using a multistage vector composed of mesoporous silicon particles (stage 1 microparticles, S1MP) loaded with neutral nanoliposomes (dioleoyl phosphatidylcholine, DOPC) containing small interfering RNA (siRNA) targeted against the EphA2 oncoprotein, which is overexpressed in most cancers, including ovarian. Our delivery methods resulted in sustained EphA2 gene silencing for at least 3 weeks in two independent orthotopic mouse models of ovarian cancer following a single i.v. administration of S1MP loaded with EphA2-siRNA-DOPC. Furthermore, a single administration of S1MP loaded with-EphA2-siRNA-DOPC substantially reduced tumor burden, angiogenesis, and cell proliferation compared with a noncoding control siRNA alone (SKOV3ip1, 54%; HeyA8, 57%), with no significant changes in serum chemistries or in proinflammatory cytokines. In summary, we have provided the first in vivo therapeutic validation of a novel, multistage siRNA delivery system for sustained gene silencing with broad applicability to pathologies beyond ovarian neoplasms. Cancer Res; 70(9); 3687–96. ©2010 AACR. |
| Databáze: | OpenAIRE |
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