Lee, Sangbin Kim, Jiyeon Shim, Gayong Kim, Sunil Han, Su Eun Kim, Kwangmeyung Kwon, Ick Chan Choi, Yongseok Kim, Young Bong Kim, Chan-Wha Oh, Yu-Kyoung 2024-01-20T13:30:44Z 2024-01-20T13:30:44Z 2021-09-04 2012-12-10 0168-3659 https://pubs.kist.re.kr/handle/201004/128552 Nanoparticles have demonstrated potential for promoting drug delivery to tumor sites and enhancing uptake. Here, we report tetraiodothyroacetic acid (tetrac) as a promising new targeting moiety for delivery of anticancer drugs to tumor tissues. Tetrac, an antagonist that blocks the binding of thyroid hormone to integrin alpha v beta 3, was covalently linked to the activated end of pegylated lipid and used to formulate tetrac-tagged pegylated liposomes (TPL). After incubating with TPL for 9 h, cellular accumulation efficiency into A375 human melanoma cells, which express integrin alpha v beta 3 at high density, was high (98.5% +/- 0.5% of cells), whereas that in KB cells, which express integrin at a very low density, was much lower (35.1% +/- 4.5%). Molecular imaging revealed that TPL preferentially distributed to tumor tissues after systemic administration in mice, where as non-targeting pegylated liposomes were distributed to tumors at background levels. Treatment with the alkyl lysophospholipid anticancer drug edelfosine, encapsulated in TPL, significantly reduced the survival of A375 tumor cells compared to cells treated with edelfosine in pegylated liposomes or with lysophosphatidylcholine encapsulated in TPL. Moreover, intravenous administration of edelfosine in TPL significantly reduced the growth of tumors and prolonged the survival of A375-xenografted mice, providing 100% protection for up to 50 days and some protection until 66 days (0% survival endpoint). In contrast, no untreated mice or mice treated with edelfosine-loaded pegylated liposomes survived up to 50 or 48 days, respectively, after tumor inoculation. These results suggest the potential of tetrac as a new ligand moiety for enhancing the delivery of anticancer drug-loaded nanoparticles to tumors and enhancing the therapeutic efficacy of encapsulated anticancer drugs. (c) 2012 Elsevier B.V. All rights reserved. English ELSEVIER SCIENCE BV LIPID RAFTS GROWTH-FACTOR BIOLOGICAL IMPLICATIONS INTRACELLULAR DELIVERY ANTITUMOR-ACTIVITY CANCER-PATIENTS CELL-SURFACE IN-VITRO EXPRESSION NANOPARTICLES Tetraiodothyroacetic acid-tagged liposomes for enhanced delivery of anticancer drug to tumor tissue via integrin receptor Article 10.1016/j.jconrel.2012.05.043 1 JOURNAL OF CONTROLLED RELEASE, v.164, no.2, pp.213 - 220 JOURNAL OF CONTROLLED RELEASE 164 2 213 220 scie scopus 000312947500014 2-s2.0-84869493371 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article LIPID RAFTS GROWTH-FACTOR BIOLOGICAL IMPLICATIONS INTRACELLULAR DELIVERY ANTITUMOR-ACTIVITY CANCER-PATIENTS CELL-SURFACE IN-VITRO EXPRESSION NANOPARTICLES Tetraiodothyroacetic acid Integrin receptor Liposome Anticancer drug Edelfosine