Tumor vasculature targeting following co-delivery of heparin-taurocholate conjugate and suberoylanilide hydroxamic acid using cationic nanolipoplex

Title
Tumor vasculature targeting following co-delivery of heparin-taurocholate conjugate and suberoylanilide hydroxamic acid using cationic nanolipoplex
Authors
김지영심가영최현우박주호정성우김선일김광명권익찬김찬하김상윤Victor C. Yang오유경변영로
Keywords
Heparin-taurocholate conjugate; Angiogenesis inhibitor; Histone deacetylase inhibitor; Tumor vasculature targeting; Cationic nanolipoplex
Issue Date
2012-06
Publisher
Biomaterials
Citation
VOL 33, NO 17, 4424-4430
Abstract
The chemical conjugate of low molecular weight heparin with taurocholate (LHT7) was previously designed to offer anticancer activity while minimizing the anticoagulant activity. In the present study, we found that the systemic administration of LHT7 in nanolipoplex could substantially enhance tumor vasculature targeting and anticancer effects. Moreover, we found that co-delivery of LHT7 with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, in nanolipoplex could provide synergistic antitumor effect. LHT7/SAHA nanolipoplex was formulated by encapsulating SAHA inside cationic liposomes, followed by complexation of negatively charged LHT7 onto the cationic surfaces of SAHA-loaded liposomes (SAHA-L). LHT7/SAHA nanolipoplex was positively charged with a mean diameter of 117.6 nm, and stable in serum. The nanolipoplex form of LHT7 could alter its pharmacokinetics and biodistribution. Compared to the free form of LHT7, LHT7 in the nanolipoplex showed 1.9-fold higher mean residence time, and higher tumor vasculature accumulation after its intravenous administration. LHT7/SAHA nanolipoplex showed highest antitumor efficacy in SCC-bearing mice, compared to LHT7, SAHA-L and sequential co-administration of LHT7 and SAHA-L. Consistent with the enhanced antitumor effect, the reduction of abnormal vessels in the tumor site was also the highest in the LHT7/ SAHA nanolipoplex-treated group. These results suggested the potential of LHT7/SAHA nanolipoplex for enhanced tumor vasculature targeting, and the importance of nanolipoplex-mediated co-delivery with a histone deacetylase inhibitor for maximal anticancer effect.
URI
http://pubs.kist.re.kr/handle/201004/43324
ISSN
01429612
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KIST Publication > Article
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