Trilysinoyl oleylamide-based cationic liposomes for systemic co-delivery of siRNA and an anticancer drug

Gayong Shim, Su Eun Han, Yong Hee Yu, Sangbin Lee, Han Young Lee, Kwang Meyung Kim, Ick Chan Kwon, Tae Gwan Park, Young Bong Kim, Yongseok Choi, Chan Wha Kim, Yu Kyoung Oh

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Oligolysine-based cationic lipid derivatives were synthesized for delivery of siRNA, and formulated into cationic liposomes. Among various oligolysine-based lipid derivatives differing in lysine residue number and lipid moiety, trilysinoyl oleylamide (TLO)-based liposomes (TLOL) showed the highest delivery efficiency combined with minimal cytotoxicity. Delivery of siRNA using TLOL silenced target genes both in vitro and in vivo. In green fluorescent protein (GFP)-expressing tumor tissue, a significant reduction of fluorescence was observed after intratumoral administration of siGFP using TLOL compared with control siGL2. Intravenous administration of siMcl1 employing pegylated TLOL (pTLOL) reduced the expression of human Mcl1 protein in KB-xenografted tumor tissue. Despite the reduction in target protein Mcl1 expression following such systemic delivery, tumor growth was only slightly reduced compared to a siGL2-treated control group. To potentiate the anticancer activity of siMcl1, the anticancer drug suberoylanilide hydroxamic acid (SAHA) was additionally encapsulated in pTLOL. After intravenous administration of siMcl1 using SAHA-loaded pTLOL (pSTLOL), a significant reduction in tumor growth was observed compared to that seen in animals treated with free SAHA or siGL2 complexed with pSTLOL. The results indicate that pTLOL could be further developed as a systemic delivery system for synergistic anticancer siRNA and a drug.

Original languageEnglish
Pages (from-to)60-66
Number of pages7
JournalJournal of Controlled Release
Volume155
Issue number1
DOIs
Publication statusPublished - 2011 Oct 10

Fingerprint

Liposomes
Small Interfering RNA
Pharmaceutical Preparations
Lipids
Intravenous Administration
Neoplasms
Growth
Green Fluorescent Proteins
Lysine
Proteins
Fluorescence
oleylamide
Control Groups
Genes
vorinostat

Keywords

  • Cationic liposome
  • Co-delivery
  • siRNA
  • Suberoylanilide hydroxamic acid
  • Trilysinoyl oleylamide

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Trilysinoyl oleylamide-based cationic liposomes for systemic co-delivery of siRNA and an anticancer drug. / Shim, Gayong; Han, Su Eun; Yu, Yong Hee; Lee, Sangbin; Lee, Han Young; Kim, Kwang Meyung; Kwon, Ick Chan; Park, Tae Gwan; Kim, Young Bong; Choi, Yongseok; Kim, Chan Wha; Oh, Yu Kyoung.

In: Journal of Controlled Release, Vol. 155, No. 1, 10.10.2011, p. 60-66.

Research output: Contribution to journalArticle

Shim, Gayong ; Han, Su Eun ; Yu, Yong Hee ; Lee, Sangbin ; Lee, Han Young ; Kim, Kwang Meyung ; Kwon, Ick Chan ; Park, Tae Gwan ; Kim, Young Bong ; Choi, Yongseok ; Kim, Chan Wha ; Oh, Yu Kyoung. / Trilysinoyl oleylamide-based cationic liposomes for systemic co-delivery of siRNA and an anticancer drug. In: Journal of Controlled Release. 2011 ; Vol. 155, No. 1. pp. 60-66.
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AU - Yu, Yong Hee

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AU - Lee, Han Young

AU - Kim, Kwang Meyung

AU - Kwon, Ick Chan

AU - Park, Tae Gwan

AU - Kim, Young Bong

AU - Choi, Yongseok

AU - Kim, Chan Wha

AU - Oh, Yu Kyoung

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AB - Oligolysine-based cationic lipid derivatives were synthesized for delivery of siRNA, and formulated into cationic liposomes. Among various oligolysine-based lipid derivatives differing in lysine residue number and lipid moiety, trilysinoyl oleylamide (TLO)-based liposomes (TLOL) showed the highest delivery efficiency combined with minimal cytotoxicity. Delivery of siRNA using TLOL silenced target genes both in vitro and in vivo. In green fluorescent protein (GFP)-expressing tumor tissue, a significant reduction of fluorescence was observed after intratumoral administration of siGFP using TLOL compared with control siGL2. Intravenous administration of siMcl1 employing pegylated TLOL (pTLOL) reduced the expression of human Mcl1 protein in KB-xenografted tumor tissue. Despite the reduction in target protein Mcl1 expression following such systemic delivery, tumor growth was only slightly reduced compared to a siGL2-treated control group. To potentiate the anticancer activity of siMcl1, the anticancer drug suberoylanilide hydroxamic acid (SAHA) was additionally encapsulated in pTLOL. After intravenous administration of siMcl1 using SAHA-loaded pTLOL (pSTLOL), a significant reduction in tumor growth was observed compared to that seen in animals treated with free SAHA or siGL2 complexed with pSTLOL. The results indicate that pTLOL could be further developed as a systemic delivery system for synergistic anticancer siRNA and a drug.

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