An Improved D-α-Tocopherol-Based Nanocarrier for Targeted Delivery of Doxorubicin with Reversal of Multidrug Resistance
dc.contributor.author | Lu, Jianqin | |
dc.contributor.author | Zhao, Wenchen | |
dc.contributor.author | Liu, Hao | |
dc.contributor.author | Marquez, Rebecca T. | |
dc.contributor.author | Huang, Yixian | |
dc.contributor.author | Zhang, Yifei | |
dc.contributor.author | Li, Jiang | |
dc.contributor.author | Xie, Wen | |
dc.contributor.author | Venkataramanan, Raman | |
dc.contributor.author | Xu, Liang | |
dc.contributor.author | Li, Song | |
dc.date.accessioned | 2017-03-17T20:10:16Z | |
dc.date.available | 2017-03-17T20:10:16Z | |
dc.date.issued | 2014-10-24 | |
dc.identifier.citation | Lu, Jianqin, Wenchen Zhao, Hao Liu, Rebecca Marquez, Yixian Huang, Yifei Zhang, Jiang Li, Wen Xie, Raman Venkataramanan, Liang Xu, and Song Li. "An Improved D-α-tocopherol-based Nanocarrier for Targeted Delivery of Doxorubicin with Reversal of Multidrug Resistance." Journal of Controlled Release 196 (2014): 272-86. | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23439 | |
dc.description.abstract | Nanocarriers have recently emerged as an attractive platform for delivery of various types of therapeutics including anticancer agents. Previously, we developed an improved TPGS delivery system (PEG5K-VE2) which demonstrated improved colloidal stability and greater in vivo antitumor activity. Nevertheless, the application of this system is still limited by a relatively low drug loading capacity (DLC). In this study we report that incorporation of a fluorenylmethyloxycarbonyl (Fmoc) motif at the interfacial region of PEG5K-VE2 led to significant improvement of the system through the introduction of an additional mechanism of drug/carrier interaction. Doxorubicin (DOX) could be effectively loaded into PEG5K-Fmoc-VE2 micelles at a DLC of 39.9%, which compares favorably to most reported DOX nanoformulations. In addition, PEG5K-Fmoc-VE2/DOX mixed micelles showed more sustained release of DOX in comparison to the counterpart without Fmoc motif. MTT assay showed that PEG5K-Fmoc-VE2/DOX exerted significantly higher levels of cytotoxicity over DOX, Doxil as well as PEG5K-VE2/DOX in PC-3 and 4T1.2 cells. Cytotoxicity assay with NCI/ADR-RES, a drug resistant cell line, suggested that PEG5K-Fmoc-VE2 may have a potential to reverse the multidrug resistance, which was supported by its inhibition on P-gp ATPase. Pharmacokinetics (PK) and biodistribution studies showed an increased half-life in blood circulation and more effective tumor accumulation for DOX formulated in PEG5K-Fmoc-VE2 micelles. More importantly, DOX-loaded PEG5K-Fmoc-VE2 micelles showed an excellent safety profile with a MTD (~30 mg DOX/kg) that is about 3 times as much as that for free DOX. Finally, superior antitumor activity was demonstrated for PEG5K-Fmoc-VE2/DOX in both drug-sensitive (4T1.2 and PC-3) and drug-resistant (KB 8-5) tumor models compared to DOX, Doxil, and PEG5K-VE2/DOX. | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
dc.subject | Fluorenylmethyloxycarbonyl | en_US |
dc.subject | Drug-interactive motif | en_US |
dc.subject | Nanomedicine | en_US |
dc.subject | Reversal of multidrug resistance | en_US |
dc.subject | Chemotherapeutics | en_US |
dc.title | An Improved D-α-Tocopherol-Based Nanocarrier for Targeted Delivery of Doxorubicin with Reversal of Multidrug Resistance | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Xu, Liang | |
kusw.kudepartment | Molecular Biosciences | en_US |
dc.identifier.doi | 10.1016/j.jconrel.2014.10.016 | en_US |
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 |
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Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.