Abstract：
: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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Tanaka T,Mangala LS,Vivas-Mejia PE,Nieves-Alicea R,Mann AP,Mora E,Han HD,Shahzad MM,Liu X,Bhavane R,Gu J,Fakhoury JR,Chiappini C,Lu C,Matsuo K,Godin B,Stone RL,Nick AM,Lopez-Berestein G,Sood AK,Ferrari Mdoi
10.1158/0008-5472.CAN-09-3931subject
Has Abstractpub_date
2010-05-01 00:00:00pages
3687-96issue
9eissn
0008-5472issn
1538-7445pii
70/9/3687journal_volume
70pub_type
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