Ligand-modified gene carriers increased uptake in target cells but reduced DNA release and transfection efficiency.
Ligand-modified gene carriers increased uptake in target cells but reduced DNA release and transfection efficiency.
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DOI：
10.1016/j.nano.2009.09.001
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发表时间：
2010-04
影响因子：
5.4
通讯作者：
Saltzman, W. Mark
中科院分区：
文献类型：
--
作者：
Cu, Yen;LeMoellic, Cathy;Caplan, Michael J.;Saltzman, W. Mark
通过使用由生物可降解聚合物如PLGA制成的颗粒载体，可以改善DNA向细胞的递送。据推测，向颗粒表面添加靶向部分以促进摄取可以进一步增强特定细胞或组织中的基因表达。利用肠和肾上皮细胞中众所周知的受体/配体相互作用，我们配制了具有高密度表面结合BSA的PLGA颗粒（约768个分子/颗粒）。BSA包被的颗粒表现出显着更高的吸收细胞表达白蛋白受体，巨蛋白，并在低pH值下抵抗降解。然而，从BSA包被的颗粒的基因表达比未改性的颗粒低3至10倍，这种转染效率的降低可能是由于从改性颗粒的DNA释放速率较慢。在这种情况下，向粒子添加目标特性会降低其有效性。我们的研究强调了在聚合物药物载体的设计中细胞摄取和有效载荷释放之间的相互作用的重要性。
DNA delivery to cells can be improved by using particle carriers made from biodegradable polymers such as PLGA. It is speculated that addition of targeting moieties to the particle surface to facilitate uptake can further enhance gene expression in specific cells or tissues. Taking advantage of well-known receptor/ligand interactions in intestinal and renal epithelial cells, we formulated PLGA particles with high density of surface-bound BSA (∼768 molecules/particle). BSA-coated particles exhibited significantly higher uptake by cells expressing the albumin receptor, megalin, and resisted degradation in low pH. However, gene expression from BSA-coated particles was 3 to 10-fold lower than unmodified particles; this reduction in transfection efficiency was probably due to the slower DNA release rate from modified particles. In this setting, addition of a targeting feature to particles reduced their effectiveness. Our study highlights the importance of the interplay between cell uptake and payload release in the design of polymer drug carriers.
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