Zaremba-Czogalla Magdalena, Jaromin Anna, Sidoryk Katarzyna, Zagórska Agnieszka, Cybulski Marcin, Gubernator Jerzy
Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14a, 50-383 Wroclaw, Poland.
Department of Pharmacy, Cosmetic Chemicals and Biotechnology, Team of Chemistry, Łukasiewicz Research Network-Industrial Chemistry Institute, 8 Rydygiera Str., 01-793 Warsaw, Poland.
Materials (Basel). 2020 Dec 19;13(24):5813. doi: 10.3390/ma13245813.
Pancreatic cancer belongs to the most aggressive group of cancers, with very poor prognosis. Therefore, there is an important need to find more potent drugs that could deliver an improved therapeutic approach. In the current study we searched for selective and effective caffeic acid derivatives. For this purpose, we analyzed twelve compounds and evaluated their in vitro cytotoxic activity against two human pancreatic cancer cell lines, along with a control, normal fibroblast cell line, by the classic MTT assay. Six out of twelve tested caffeic acid derivatives showed a desirable effect. To improve the therapeutic efficacy of such active compounds, we developed a formulation where caffeic acid derivative (7) was encapsulated into liposomes composed of soybean phosphatidylcholine and DSPE-PEG. Subsequently, we analyzed the properties of this formulation in terms of basic physical parameters (such as size, zeta potential, stability at 4 °C and morphology), hemolytic and cytotoxic activity and cellular uptake. Overall, the liposomal formulation was found to be stable, non-hemolytic and had activity against pancreatic cancer cells (IC 19.44 µM and 24.3 µM, towards AsPC1 and BxPC3 cells, respectively) with less toxicity against normal fibroblasts. This could represent a promising alternative to currently available treatment options.
胰腺癌属于侵袭性最强的癌症类型，预后极差。因此，迫切需要找到更有效的药物，以提供更好的治疗方法。在本研究中，我们寻找选择性和有效的咖啡酸衍生物。为此，我们分析了12种化合物，并通过经典的MTT法评估了它们对两种人胰腺癌细胞系以及一种对照正常成纤维细胞系的体外细胞毒性活性。12种受试咖啡酸衍生物中有6种显示出理想的效果。为了提高此类活性化合物的治疗效果，我们开发了一种制剂，将咖啡酸衍生物（7）包裹在由大豆磷脂酰胆碱和DSPE-PEG组成的脂质体中。随后，我们从基本物理参数（如大小、zeta电位、4°C下的稳定性和形态）、溶血和细胞毒性活性以及细胞摄取方面分析了该制剂的性质。总体而言，该脂质体制剂被发现是稳定的、无溶血作用的，并且对胰腺癌细胞具有活性（对AsPC1和BxPC3细胞的IC分别为19.44μM和24.3μM），对正常成纤维细胞的毒性较小。这可能是目前可用治疗方案的一个有前景的替代方案。
