School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio Campus, Finland.
Eur J Pharm Sci. 2012 Dec 18;47(5):848-56. doi: 10.1016/j.ejps.2012.09.001. Epub 2012 Sep 14.
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.
在这项研究中，亲和素-生物素技术与多功能药物载体模式（即脂质体）相结合，以实现主动和通用的靶向方法。抗癌药物阿霉素（DOX）经过直接生物素化（B-DOX）修饰（Allart 等人，2003 年），或封装在生物素化的立体稳定的 pH 敏感脂质体（BL-DOX）中，并靶向到在细胞膜上表达亲和素融合蛋白的慢病毒载体转导细胞（Lehtolainen 等人，2003 年；Lesch 等人，2009 年）。阿霉素的直接生物素化提高了表达亲和素融合蛋白受体的大鼠神经胶质瘤（BT4C）细胞的细胞内化，但由于核定位受损，细胞毒性降低了 78 倍。相比之下，脂质体制剂在几种细胞系中恢复了 DOX 的生物学活性。然而，主要由于通过非特异性途径摄取，BL-DOX 的主动靶向在体外和体内研究中都可以忽略不计。多功能药物载体系统的主动靶向具有挑战性，需要进一步研究来优化靶向药物载体和受体表达系统的特性。
