Trilysinoyl oleylamide-based cationic liposomes for systemic co-delivery of siRNA and an anticancer drug
- Title
- Trilysinoyl oleylamide-based cationic liposomes for systemic co-delivery of siRNA and an anticancer drug
- Authors
- 심가용; 한수은; 유용희; 이상빈; 이한용; 김광명; 권익찬; 박태관; 김용봉; 최용석; 김찬화; 오유경
- Keywords
- Trilysinoyl oleylamide; Cationic liposome; Co-delivery; siRNA; Suberoylanilide hydroxamic acid
- Issue Date
- 2011-10
- Publisher
- Journal of controlled release
- Citation
- VOL 155, NO 1, 60-66
- 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.
- URI
- http://pubs.kist.re.kr/handle/201004/39559
- ISSN
- 0168-3659
- Appears in Collections:
- KIST Publication > Article
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