Targeted delivery via avidin fusion protein: intracellular fate of biotinylated doxorubicin derivative and cellular uptake kinetics and biodistribution of biotinylated liposomes.
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| Abstract |
In this study, avidin-biotin technology was combined with a multifunctional drug carrier modality i.e. liposomes to achieve an active and versatile targeting approach. The anti-cancer drug doxorubicin (DOX) was modified with direct biotinylation (B-DOX) (Allart et al., 2003), or encapsulated in biotinylated sterically stabilized pH-sensitive liposomes (BL-DOX), and targeted to the lentiviral vector transduced cells expressing an avidin fusion protein on the cell membrane (Lehtolainen et al., 2003; Lesch et al., 2009). The direct biotinylation of doxorubicin improved cell internalization in rat glioma (BT4C) cells expressing avidin fusion protein receptor but cell toxicity was reduced by 78-fold due to impaired nuclear localization. In contrast, liposomal formulations restored the biological activity of the DOX in several cell lines. However, mainly due to uptake via non-specific pathways the active targeting of BL-DOX was negligible in both in vitro and in vivo studies. Active targeting with multifunctional drug carrier systems is challenging and further studies will be needed to optimize the properties of targeted drug carrier and receptor expression systems.
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| Authors | Suvi K Soininen, Pauliina Lehtolainen-Dalkilic, Tanja Karppinen, Tiina Puustinen, Galina Dragneva, Minna U Kaikkonen, Marjo Jauhiainen, Brigitte Allart, David L Selwood, Thomas Wirth, Hanna P Lesch, Ann-Marie Määttä, Jukka Mönkkönen, Seppo Ylä-Herttuala, Marika Ruponen |
| Journal | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 47 Issue 5 Pg. 848-56 (Dec 18 2012) ISSN: 1879-0720 [Electronic] Netherlands |
| PMID | 22985874 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2012 Elsevier B.V. All rights reserved. |
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