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

46 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 1

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Mitogen-Activated Protein Kinase Kinases
Liposomes
Small Interfering RNA
Tumors
Double-Stranded RNA
Cells
Neoplasms
Polymerase chain reaction
Zeta potential
Real-Time Polymerase Chain Reaction
Cell Survival
Proteins
Western Blotting
PD 0325901
Apoptosis
Lipids
Therapeutics
Growth

Keywords

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

ASJC Scopus subject areas

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

Cite this

Cationic liposomal co-delivery of small interfering RNA and a MEK inhibitor for enhanced anticancer efficacy. / Kang, Seung Hee; Cho, Hee Jeong; Shim, Gayong; Lee, Sangbin; Kim, Su Hyeon; Choi, Han Gon; Kim, Chan Wha; Oh, Yu Kyoung.

In: Pharmaceutical Research, Vol. 28, No. 12, 01.12.2011, p. 3069-3078.

Research output: Contribution to journalArticle

Kang, Seung Hee ; Cho, Hee Jeong ; Shim, Gayong ; Lee, Sangbin ; Kim, Su Hyeon ; Choi, Han Gon ; Kim, Chan Wha ; Oh, Yu Kyoung. / Cationic liposomal co-delivery of small interfering RNA and a MEK inhibitor for enhanced anticancer efficacy. In: Pharmaceutical Research. 2011 ; Vol. 28, No. 12. pp. 3069-3078.
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