Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins
Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins
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DOI：
10.1016/j.jconrel.2014.11.029
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发表时间：
2015-05-10
影响因子：
10.8
通讯作者：
Stevens, Molly M.
中科院分区：
文献类型：
--
作者：
Fuhrmann, Gregor;Serio, Andrea;Stevens, Molly M.
细胞外囊泡（EV）是由细胞内源性产生的基于磷脂的颗粒。它们的天然组成和选择性细胞相互作用使它们成为有前途的药物载体。然而，为了利用它们的特性，需要研究有效的外源性药物包封方法。在这里，生产了来自各种细胞来源（内皮细胞、癌症细胞和干细胞）的EV，并对其大小和组成进行了表征。采用不同疏水性的卟啉作为模型药物，并使用各种被动和主动方法（电穿孔、皂苷、挤出和透析）包封到EV中。使用被动孵育，疏水化合物非常有效地加载到EV中，并且比加载到由磷酸胆碱和胆固醇组成的标准脂质体中的量显著更高。此外，与游离或脂质体包封的药物相比，装载到EV中显著增加了细胞摄取>60%和疏水卟啉的体外光动力学效应。与被动方法相比，特别是皂苷辅助方法的主动封装技术允许亲水性卟啉的载药量高达11倍。在癌细胞模型中，装载有亲水性卟啉的EV比游离药物诱导更强的光毒性作用。我们的研究结果为基于直接和可转移方法的电动汽车作为智能药物载体的发展奠定了坚实的基础。(C)2014由Elsevier B.V.出版
Extracellular vesicles (EVs) are phospholipid-based particles endogenously produced by cells. Their natural composition and selective cell interactions make them promising drug carriers. However, in order to harness their properties, efficient exogenous drug encapsulation methods need to be investigated. Here, EVs from various cellular origins (endothelial, cancer and stem cells) were produced and characterised for size and composition. Porphyrins of different hydrophobicities were employed as model drugs and encapsulated into EVs using various passive and active methods (electroporation, saponin, extrusion and dialysis). Hydrophobic compounds loaded very efficiently into EVs and at significantly higher amounts than into standard liposomes composed of phosphocholine and cholesterol using passive incubation. Moreover, loading into EVs significantly increased the cellular uptake by >60% and the photodynamic effect of hydrophobic porphyrins in vitro compared to free or liposome encapsulated drug. The active encapsulation techniques, with the saponin-assisted method in particular, allowed an up to 11 fold higher drug loading of hydrophilic porphyrins compared to passive methods. EVs loaded with hydrophilic porphyrins induced a stronger phototoxic effect than free drug in a cancer cell model. Our findings create a firm basis for the development of EVs as smart drug carriers based on straightforward and transferable methods. (C) 2014 Published by Elsevier B.V.