The intracellular fate of an amphipathic pH-responsive polymer: Key characteristics towards drug delivery.
The intracellular fate of an amphipathic pH-responsive polymer: Key characteristics towards drug delivery.
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DOI：
10.1016/j.msec.2016.08.004
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发表时间：
2016-12
期刊：
影响因子：
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通讯作者：
S. Mercado;Claudia Orellana-Tavra;A. Chen;Nigel K.H. Slater
中科院分区：
文献类型：
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作者：
S. Mercado;Claudia Orellana-Tavra;A. Chen;Nigel K.H. Slater
生物聚合物通过增强其细胞内可及性和功效而成为治疗分子的重要药物递送系统。然而，这些药物穿过细胞膜的运输和它们释放到胞质溶胶中仍然是一个挑战。用骨肉瘤细胞系SAOS-2研究了接枝苯丙氨酸的聚赖氨酸异邻苯二甲酰胺（PP-50）的转运。这种两亲性生物聚合物与内吞示踪剂，如转铁蛋白和乳糖神经酰胺的共定位表明，PP-50是部分内化的网格蛋白和小窝蛋白介导的内吞作用。巨胞饮作用也进行了研究，但这种机制和PP-50运输之间的相关性较小。当细胞与内吞抑制剂预孵育时，发现聚合物介导的钙黄绿素摄取显著降低，这也表明使用细胞内化机制的组合。此外，PP-50与内体和溶酶体途径标志物的共定位表明，聚合物能够在成熟前逃离内溶酶体区室。这是生物聚合物用作药物递送系统和生物医学应用的关键特性。
Biopolymers have become important drug delivery systems for therapeutic molecules by enhancing their accessibility and efficacy intracellularly. However, the transport of these drugs across the cell membrane and their release into the cytosol remain a challenge. The trafficking of poly (l-lysine iso-phthalamide) grafted with phenylalanine (PP-50) was investigated using an osteosarcoma cell line (SAOS-2). Colocalisation of this amphipathic biopolymer with endocytosis tracers, such as transferrin and lactosylceramide, suggested that PP-50 is partially internalised by both clathrin and caveolin-mediated endocytosis. Macropinocytosis was also investigated, but a smaller correlation was found between this mechanism and PP-50 transport. A significant decrease in polymer-mediated calcein uptake was found when cells were pre-incubated with endocytosis inhibitors, suggesting also the use of a combination of mechanisms for cell internalisation. In addition, PP-50 colocalisation with endosome and lysosome pathway markers showed that the polymer was able to escape the endolysosomal compartment before maturation. This is a critical characteristic of a biopolymer towards use as drug delivery systems and biomedical applications.