Uram Łukasz, Szuster Magdalena, Misiorek Maria, Filipowicz Aleksandra, Wołowiec Stanisław, Wałajtys-Rode Elżbieta
Faculty of Chemistry, Rzeszów University of Technology, 6 Powstańców Warszawy Ave, 35-959 Rzeszów, Poland.
Faculty of Chemistry, Rzeszów University of Technology, 6 Powstańców Warszawy Ave, 35-959 Rzeszów, Poland.
Eur J Pharm Sci. 2017 May 1;102:275-283. doi: 10.1016/j.ejps.2017.03.022. Epub 2017 Mar 16.
In a search for the safe vitamin carrier the PAMAM G3 dendrimer covalently substituted with 9 and 10 molecules of vitamin B7 (biotin) and B6 (pyridoxal), respectively (BC-PAMAM) was investigated. Dendrimer substitution with B-group vitamins significantly alters its biological properties as compared to native form. Observed effects on investigated cell parameters including morphology, adhesion, migration and ATP level were different for normal human fibroblasts (BJ) and squamous cell carcinoma (SCC-15) cell lines. BC-PAMAM revealed significantly less pronounced effects on investigated parameters, particularly at higher concentrations (5-50μM), which is relevant with its lower positive surface charge, as compared with native form. The bioconjugate, up to 50μM concentration, appeared to be a safe vitamin carrier to normal fibroblasts, without significant effect on their adhesion, shape and migration as well as on intracellular ATP level. In SCC-15 cells BC-PAMAM, at low concentrations (0.1-0.5μM), altered the cell shape and increase adhesion, whereas at higher concentrations opposite effects were seen. Measurements of cellular level of ATP showed that higher resistance of cancer cells to toxic effects of native PAMAM dendrimers may be due to higher energy supply of cancer cells.
为寻找安全的维生素载体,研究了分别与9个和10个维生素B7(生物素)分子及B6(吡哆醛)分子共价取代的PAMAM G3树枝状大分子(BC-PAMAM)。与天然形式相比,用B族维生素取代树枝状大分子会显著改变其生物学特性。对于正常人成纤维细胞(BJ)和鳞状细胞癌(SCC-15)细胞系,观察到的对包括形态、黏附、迁移和ATP水平在内的研究细胞参数的影响有所不同。与天然形式相比,BC-PAMAM对研究参数的影响明显较小,尤其是在较高浓度(5-50μM)时,这与其较低的正表面电荷有关。浓度高达50μM时,该生物共轭物对正常成纤维细胞似乎是一种安全的维生素载体,对其黏附、形状和迁移以及细胞内ATP水平均无显著影响。在SCC-15细胞中,低浓度(0.1-0.5μM)的BC-PAMAM会改变细胞形状并增加黏附,而在较高浓度时则会出现相反的效果。细胞ATP水平的测量表明,癌细胞对天然PAMAM树枝状大分子毒性作用的较高抗性可能归因于癌细胞更高的能量供应。