Kim, Ji-young Shim, Gayong Choi, Hyun-woo Park, Jooho Chung, Seung Woo Kim, Sunil Kim, Kwangmeyung Kwon, Ick Chan Kim, Chan-Wha Kim, Sang Yoon Yang, Victor C. Oh, Yu-Kyoung Byun, Youngro 2024-01-20T14:33:59Z 2024-01-20T14:33:59Z 2021-09-05 2012-06 0142-9612 https://pubs.kist.re.kr/handle/201004/129206 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. (C) 2012 Elsevier Ltd. All rights reserved. English ELSEVIER SCI LTD HISTONE DEACETYLASE INHIBITORS CLINICAL-TRIALS CANCER-THERAPY LIPOSOMES ANGIOGENESIS LIPOPLEXES EFFICACY INCREASE VESSELS SURFACE Tumor vasculature targeting following co-delivery of heparin-taurocholate conjugate and suberoylanilide hydroxamic acid using cationic nanolipoplex Article 10.1016/j.biomaterials.2012.02.066 1 BIOMATERIALS, v.33, no.17, pp.4424 - 4430 BIOMATERIALS 33 17 4424 4430 scie scopus 000303181500019 2-s2.0-84862809560 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article HISTONE DEACETYLASE INHIBITORS CLINICAL-TRIALS CANCER-THERAPY LIPOSOMES ANGIOGENESIS LIPOPLEXES EFFICACY INCREASE VESSELS SURFACE Heparin-taurocholate conjugate Angiogenesis inhibitor Histone deacetylase inhibitor Cationic nanolipoplex Tumor vasculature targeting