Intravenous Delivery of Anti-RhoA Small Interfering RNA Loaded in Nanoparticles of Chitosan in Mice: Safety and Efficacy in Xenografted Aggressive Breast Cancer. - Archive ouverte HAL Access content directly
Journal Articles Human Gene Therapy Year : 2006

Intravenous Delivery of Anti-RhoA Small Interfering RNA Loaded in Nanoparticles of Chitosan in Mice: Safety and Efficacy in Xenografted Aggressive Breast Cancer.

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Abstract

Overexpression of RhoA in cancer indicates a poor prognosis, because of increased tumor cell proliferation and invasion and tumor angiogenesis. We showed previously that anti-RhoA small interfering RNA (siRNA) inhibited aggressive breast cancer more effectively than conventional blockers of Rho-mediated signaling pathways. This study reports the efficacy and lack of toxicity of intravenously administered encapsulated anti-RhoA siRNA in chitosan-coated polyisohexylcyanoacrylate (PIHCA) nanoparticles in xenografted aggressive breast cancers (MDA-MB-231). The siRNA was administered every 3 days at a dose of 150 or 1500 microg/kg body weight in nude mice. This treatment inhibited the growth of tumors by 90% in the 150- micro g group and by even more in the 1500- micro g group. Necrotic areas were observed in tumors from animals treated with anti-RhoA siRNA at 1500 micro g/kg, resulting from angiogenesis inhibition. In addition, this therapy was found to be devoid of toxic effects, as evidenced by similarities between control and treated animals for the following parameters: body weight gain; biochemical markers of hepatic, renal, and pancreatic function; and macroscopic appearance of organs after 30 days of treatment. Because of its efficacy and the absence of toxicity, it is suggested that this strategy of anti-RhoA siRNA holds significant promise for the treatment of aggressive cancers.
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Dates and versions

inserm-00091648 , version 1 (06-09-2006)

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Jean-Yves Pillé, Hong Li, Emmanuel Blot, Jean-Rémi Bertrand, Linda L. Pritchard, et al.. Intravenous Delivery of Anti-RhoA Small Interfering RNA Loaded in Nanoparticles of Chitosan in Mice: Safety and Efficacy in Xenografted Aggressive Breast Cancer.. Human Gene Therapy, 2006, 17 (10), pp.1019-1026. ⟨10.1089/hum.2006.17.ft-248⟩. ⟨inserm-00091648⟩
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