dc.contributor.author | Cai, Shuang | |
dc.contributor.author | Alhowyan, Adel Ali B. | |
dc.contributor.author | Yang, Qiuhong | |
dc.contributor.author | Forrest, W. C. Melanie | |
dc.contributor.author | Shnayder, Yelizaveta | |
dc.contributor.author | Forrest, M. Laird | |
dc.date.accessioned | 2017-03-23T19:24:17Z | |
dc.date.available | 2017-03-23T19:24:17Z | |
dc.date.issued | 2014-06-03 | |
dc.identifier.citation | Cai, Shuang, Adel Ali B. Alhowyan, Qiuhong Yang, W. C. Melanie Forrest, Yelizaveta Shnayder, and M. Laird Forrest. "Cellular Uptake and Internalization of Hyaluronan-based Doxorubicin and Cisplatin Conjugates." Journal of Drug Targeting 22.7 (2014): 648-57. | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23480 | |
dc.description.abstract | BackgroundHyaluronan (HA) is a ligand for the CD44 receptor which is crucial to cancer cell proliferation and metastasis. High levels of CD44 expression in many cancers have encouraged the development of HA-based carriers for anti-cancer therapeutics.PurposeThe objective of this study was to determine whether HA conjugation of anticancer drugs impacts CD44-specific HA-drug uptake and disposition by human head and neck cancer cells.MethodsThe internalization and cellular disposition of hyaluronan-doxorubicin (HA-DOX), hyaluronan-cisplatin (HA-Pt), and hyaluronan-cyanine7 (HA-Cy7) conjugates were investigated by inhibiting endocytosis pathways, and by inhibiting the CD44–mediated internalization pathways that are known to mediate hyaluronan uptake in vitro.ResultsCellular internalization of HA was regulated by CD44 receptors. In mouse xenografts, HA conjugation significantly enhanced tumor cell uptake compared to unconjugated drug.DiscussionThe results suggested that the main mechanism of HA-based conjugate uptake may be active transport via CD44 in conjunction with a clathrin–dependent endocytic pathway. Other HA receptors, hyaluronan–mediated motility receptor (RHAMM) and lymphatic vessel endothelial hyaluronan receptor (LYVE-1), did not play a significant role in conjugate uptake.ConclusionsHA conjugation significantly increased CD44 mediated drug uptake and extended the residence time of drugs in tumor cells. | en_US |
dc.publisher | Informa Healthcare | en_US |
dc.rights | Copyright Informa Healthcare | en_US |
dc.subject | Hyaluronan | en_US |
dc.subject | Doxorubicin | en_US |
dc.subject | Cisplatin | en_US |
dc.subject | Internalization mechanism | en_US |
dc.subject | CD44 receptors | en_US |
dc.title | Cellular Uptake and Internalization of Hyaluronan-based Doxorubicin and Cisplatin Conjugates | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Forrest, M. Laird | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
dc.identifier.doi | 10.3109/1061186X.2014.921924 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-7658-1647 | |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess | |