Division of Drugs, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Int J Pharm. 2012 Feb 28;423(2):401-9. doi: 10.1016/j.ijpharm.2011.12.022. Epub 2011 Dec 23.
New technologies are needed to deliver medicines safely and effectively. Polymeric nanoparticulate carriers are one such technology under investigation. We examined the intracellular trafficking of doxorubicin-bound block copolymers quantitatively and by imaging doxorubicin-derived fluorescence using confocal microscopy. The polymers were internalized by endocytosis and distributed in endosomal/lysosomal compartments and the endoplasmic reticulum; unlike free doxorubicin, the polymers were not found in the nucleus. Moreover, the ATP-binding cassette protein B1 (ABCB1) transporter may be involved in the efflux of the polymer from cells. This drug delivery system is attractive because the endogenous transport system is used for the uptake and delivery of the artificial drug carrier to the target as well as for its efflux from cells to medium. Our results show that a drug delivery system strategy targeting this endogenous transport pathway may be useful for affecting specific molecular targets.
需要新技术来安全有效地输送药物。聚合纳米颗粒载体就是正在研究的一种技术。我们通过共焦显微镜定量检查和成像阿霉素衍生荧光来研究阿霉素结合嵌段共聚物的细胞内转运。聚合物通过内吞作用被内化，并分布在内涵体/溶酶体和内质网中；与游离阿霉素不同，聚合物不在细胞核中发现。此外，三磷酸腺苷结合盒蛋白 B1（ABCB1）转运蛋白可能参与聚合物从细胞中的外排。这种药物输送系统很有吸引力，因为内源性转运系统用于将人工药物载体摄取和递送到靶标，以及将其从细胞外排到培养基中。我们的结果表明，针对这种内源性转运途径的药物输送系统策略可能有助于影响特定的分子靶标。
