Cationic liposomal co-delivery of small interfering RNA and a MEK inhibitor for enhanced anticancer efficacy

Seung Hee Kang, Hee Jeong Cho, Gayong Shim, Sangbin Lee, Su Hyeon Kim, Han Gon Choi, Chan Wha Kim, Yu Kyoung Oh

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Purpose: 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. Method: 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. Results: 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. Conclusions: PDGL-mediated co-delivery of siMcl1 and MEK inhibitor, PD0325901, could serve as a potential strategy for combination chemogene anticancer therapy.

Original languageEnglish
Pages (from-to)3069-3078
Number of pages10
JournalPharmaceutical research
Volume28
Issue number12
DOIs
Publication statusPublished - 2011 Dec

Keywords

  • MEK inhibitor
  • co-delivery
  • combination therapy
  • liposome
  • siRNA

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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    Kang, S. H., Cho, H. J., Shim, G., Lee, S., Kim, S. H., Choi, H. G., Kim, C. W., & Oh, Y. K. (2011). Cationic liposomal co-delivery of small interfering RNA and a MEK inhibitor for enhanced anticancer efficacy. Pharmaceutical research, 28(12), 3069-3078. https://doi.org/10.1007/s11095-011-0569-4