Aharon Danor, Weitman Hana, Ehrenberg Benjamin
Department of Physics and Institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan, Israel.
Biochim Biophys Acta. 2011 Aug;1808(8):2031-5. doi: 10.1016/j.bbamem.2011.03.015. Epub 2011 Apr 5.
Hematoporphyrin is being used as a photosensitizer in photodynamic therapy of tumors, as well as of other clinical cases. Many classes of tetrapyrroles, including hematoporphyrin, are partitioning quite easily into the external cytoplasmic membrane as the mechanism of cellular uptake. Several chemical and physical parameters of the membrane were studied for their effect on the extent of porphyrins' partitioning. In this manuscript we report, for the first time, a quantitative analysis of the effect of the membrane's surface electric potential on the partitioning. We prepared liposomes, as membrane models, composed on zwitterionic DMPC lipid, as well as DMPC liposomes that contain a small, varying fraction of negatively charged DMPS and positively charged DOTAP. We found that indeed the surface potential had a very strong effect on the binding constant of HP, which is negatively charged at the physiological pH that was used. The trend in the apparent binding constant can be formulated and fitted with the Gouy-Chapman model of surface potential. We found that the average concentration of HP within the aqueous shell that has a thickness of the Debye layer around the liposome is determining the extent of binding in the law of mass action.
血卟啉正被用作肿瘤以及其他临床病例光动力治疗中的光敏剂。包括血卟啉在内的几类四吡咯很容易通过细胞摄取机制进入外细胞膜。研究了膜的几个化学和物理参数对卟啉分配程度的影响。在本论文中，我们首次报道了膜表面电势对分配影响的定量分析。我们制备了脂质体作为膜模型，其由两性离子DMPC脂质组成，以及含有少量不同比例带负电荷的DMPS和带正电荷的DOTAP的DMPC脂质体。我们发现表面电势确实对血卟啉（在所用生理pH下带负电荷）的结合常数有非常强烈的影响。表观结合常数的趋势可以用表面电势的古依-查普曼模型来表述和拟合。我们发现，在脂质体周围具有德拜层厚度的水相中血卟啉的平均浓度决定了质量作用定律中的结合程度。
