Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wroclaw University of Science and Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland.
Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-367 Wroclaw, Poland; Department of Molecular and Cellular Biology, Wroclaw Medical University, Borowska 211 A, 50-556 Wroclaw, Poland.
J Colloid Interface Sci. 2018 Jul 15;522:163-173. doi: 10.1016/j.jcis.2018.03.063. Epub 2018 Mar 20.
We designed novel polymer-free cubic bicontinuous liquid crystalline dispersions (cubosomes) using monoolein as molecular building block, phospholipids as stabilizers, propylene glycol as hydrotrope. Their kinetic stability was evaluated by analysing the backscattering profiles upon ageing, and the most stable formulation was chosen as potential photosensitizers delivery vehicle for photodynamic therapy (PDT) of human skin melanoma cells. Morphological and topological features of such formulation alternatively loaded with Chlorin e6 or meso-Tetraphenylporphine-Mn(III) chloride photosensitizing dyes were investigated by cryo-TEM, DLS, and SAXS. Bioimaging studies demonstrated that Me45 and MeWo cell lines effectively internalized these cubosomes formulations. Particularly, photodynamic activity experiments proved both the very low cytotoxicity of the cubosomes formulation loaded with Chlorin e6 dye in the "dark" condition, and its significant cytotoxic effect after photoirradiation. The toxic effect recorded when the photosensitizer was encapsulated within the cubosomes was shown to be one order of magnitude higher than that caused by the free photosensitizer. This is the first report of biocompatible polymer-free cubosomes for potential application in both PDT and bioimaging of skin malignant melanoma.
我们设计了一种新型的无聚合物立方双连续液晶分散体(立方脂质体),使用单油酸甘油酯作为分子构建块,磷脂作为稳定剂,丙二醇作为助溶剂。通过分析老化过程中的反向散射谱来评估其动力学稳定性,并选择最稳定的配方作为潜在的光敏剂输送载体,用于人皮肤黑色素瘤细胞的光动力疗法(PDT)。通过低温透射电子显微镜、动态光散射和小角 X 射线散射研究了这种交替负载氯己定或间四苯基卟啉-Mn(III)氯化物光敏染料的制剂的形态和拓扑特征。生物成像研究表明,Me45 和 MeWo 细胞系有效地内化了这些立方脂质体制剂。特别是,光动力活性实验证明了负载氯己定染料的立方脂质体制剂在“黑暗”条件下的细胞毒性非常低,而在光照后具有显著的细胞毒性作用。当将光敏剂封装在立方脂质体中时,记录到的毒性作用比游离光敏剂高一个数量级。这是首例关于生物相容性无聚合物立方脂质体的报告,可潜在应用于皮肤恶性黑色素瘤的 PDT 和生物成像。