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
심가용한수은유용희이상빈이한용김광명권익찬박태관김용봉최용석김찬화오유경
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
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KIST Publication > Article
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