Effects of poly-(lactide-co-glycolide) nanoparticles on electrophysiological properties of enteroendocrine cells.
Effects of poly-(lactide-co-glycolide) nanoparticles on electrophysiological properties of enteroendocrine cells.
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DOI：
10.1166/jnn.2011.3802
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发表时间：
2011-04
影响因子：
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通讯作者：
B. Shah;S. Kona;T. Gilbertson;K. Nguyen
中科院分区：
文献类型：
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作者：
B. Shah;S. Kona;T. Gilbertson;K. Nguyen
PLGA纳米颗粒被广泛用于将药理学化合物和基因递送到各种细胞类型。尽管事实上这些细胞类型中的许多严重依赖于离子通道活性以正常发挥功能，但尚未研究纳米颗粒对离子通道活性的影响。为此，我们研究了纳米颗粒对胆囊收缩素（CCK）释放肠内分泌细胞（EEC）系STC-1的影响。研究表明，STC-1细胞对食物反应时CCK释放的调节依赖于这些细胞的正常产电特性，包括电压门控钙和钾通道的活性。由于电压门控离子通道在STC-1细胞的正常生理反应中的重要性，我们进行了电生理（膜片钳）实验来评估PLGA纳米颗粒对电压门控钙和钾通道的影响。在含有100 nm纳米颗粒的STC-1细胞上的全细胞膜片钳记录显示钙和钾通道活性没有肉眼可见的差异。其他实验确定，这些电压门控离子通道的激活、失活和使用依赖性失活对纳米颗粒的这些基本生物物理性质没有任何显著影响。最后，我们研究了PLGA纳米颗粒对刺激诱导的STC-1细胞内钙离子浓度升高的影响，这是释放CCK所必需的。我们的数据表明，使用PLGA纳米颗粒没有改变STC-1细胞的电生理特性，并支持使用PLGA纳米颗粒作为一种有吸引力的选择，用于将药物/基因递送到消化系统的细胞，最终可能被证明可用于减少食欲/食物摄入和治疗各种胃肠道疾病。
PLGA nanoparticles are widely used to deliver pharmacological compounds and genes to a variety of cell types. Despite the fact that many of these cells types depend critically on ion channel activity to function normally, there have been no studies on the effect of nanoparticles on the ion channel activity. To this end, we have investigated the effect of nanoparticles on cholecystokinin (CCK)-releasing enteroendocrine cell (EEC) line STC-1. It has been shown that regulation of CCK release from STC-1 cells in response to food depends on the normal electrogenic properties of these cells, including the activity of voltage-gated calcium and potassium channels. Due to the importance of voltage-gated ion channels in the normal physiological responses of STC-1 cells, we performed electrophysiological (patch clamp) experiments to assess the effects of PLGA nanoparticles on the voltage-gated calcium and potassium channels. Whole-cell patch clamp recordings on STC-1 cells containing 100 nm nanoparticles show no macroscopic differences in calcium and potassium channel activity. Additional experiments determined that the activation, inactivation, and use-dependent inactivation of these voltage-gated ion channels did not have any significant effect of nanoparticles on these basic biophysical properties. Lastly, we have examined the effects of PLGA nanoparticles on stimulus-induced rise in intracellular calcium concentration in STC-1 cells, which is necessary for release of CCK. Our data demonstrate that the use of PLGA nanoparticles did not alter the electrophysiological properties of STC-1 cells and supports the use of PLGA nanoparticles as an attractive option for delivering pharmaceuticals/genes to cells of the digestive system that might eventually prove useful for reducing appetite/food intake and in treatment of various gastrointestinal illnesses.