Cationic Liposomal Co-delivery of Small Interfering RNA and a MEK Inhibitor for Enhanced Anticancer Efficacy
- Authors
- Kang, Seung Hee; Cho, Hee-Jeong; Shim, Gayong; Lee, Sangbin; Kim, Su-Hyeon; Choi, Han-Gon; Kim, Chan-Wha; Oh, Yu-Kyoung
- Issue Date
- Dec-2011
- Publisher
- SPRINGER/PLENUM PUBLISHERS
- Keywords
- co-delivery; combination therapy; liposome; MEK inhibitor; siRNA
- Citation
- PHARMACEUTICAL RESEARCH, v.28, no.12, pp.3069 - 3078
- Indexed
- SCIE
SCOPUS
- Journal Title
- PHARMACEUTICAL RESEARCH
- Volume
- 28
- Number
- 12
- Start Page
- 3069
- End Page
- 3078
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/36362
- DOI
- 10.1007/s11095-011-0569-4
- ISSN
- 0724-8741
- Abstract
- To test whether co-delivery of anticancer small interfering RNA (siRNA) and a chemical MEK inhibitor using cationic liposomes enhances anticancer activity in vitro and in vivo. MEK inhibitor PD0325901 was encapsulated in lipid layers of N',N''-dioleylglutamide-based cationic liposomes (DGL). Mcl1-specific siRNA (siMcl1) was complexed to DGL or PD0325901-loaded liposomes (PDGL). Efficiency of cellular siRNA delivery was tested using fluorescent double-stranded RNA. Silencing of target proteins was evaluated using Western blotting and real-time quantitative polymerase chain reactions. In vivo anticancer activity was tested using xenografted mice. Size and zeta potential of PDGL were similar to DGL. PDGL could deliver double-stranded RNA into cells with efficiencies comparable to DGL. Cellular co-delivery of siMcl1 and PD0325901 reduced expression of Mcl1 and pERK1/2 proteins and more effectively reduced tumor cell survival than other treatments. In mice, siMcl1 and PD0325901 co-delivered by PDGL inhibited growth of tumors 79%. Substantial apoptosis of tumor cells was observed following PDGL-mediated co-delivery of siMcl1, but not in other groups. PDGL-mediated co-delivery of siMcl1 and MEK inhibitor, PD0325901, could serve as a potential strategy for combination chemogene anticancer therapy.
- Files in This Item
-
Go to Link
- Appears in
Collections - COLLEGE OF PHARMACY > DEPARTMENT OF PHARMACY > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/36362)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.