Exploring the Interactions of Ruthenium (II) Carbosilane Metallodendrimers and Precursors with Model Cell Membranes through a Dual Spin-Label Spin-Probe Technique Using EPR

Biomolecules

卷:9

Natalia Sanz del Olmo¹  Paula Ortega¹  F.Javier de la Mata¹  Rafael Gómez¹  Sandra García-Gallego¹  Alberto Fattori²  Michela Cangiotti²  Riccardo Carloni²  MariaFrancesca Ottaviani² 

[1] Department of Organic and Inorganic Chemistry, and Research Institute in Chemistry “Andrés M. del Río” (IQAR), University of Alcalá, 28805 Madrid, Spain;

[2] Department of Pure and Applied Sciences, University of Urbino “Carlo Bo”, 61029 Urbino, Italy;

关键词: electron paramagnetic resonance;    dendrimer;    metallodendrimer;    ruthenium;    cell membrane;    spin probe;    cancer;   

DOI  :  10.3390/biom9100540

来源: DOAJ

【 摘 要 】

Dendrimers exhibit unique interactions with cell membranes, arising from their nanometric size and high surface area. To a great extent, these interactions define their biological activity and can be reported in situ by spin-labelling techniques. Schiff-base carbosilane ruthenium (II) metallodendrimers are promising antitumor agents with a mechanism of action yet to explore. In order to study their in situ interactions with model cell membranes occurring at a molecular level, namely cetyltrimethylammonium bromide micelles (CTAB) and lecithin liposomes (LEC), electron paramagnetic resonance (EPR) was selected. Both a spin probe, 4-(N,N-dimethyl-N-dodecyl)ammonium-2,2,6,6-tetramethylpiperidine-1-oxyl bromide (CAT12), able to enter the model membranes, and a spin label, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) covalently attached at newly synthesized heterofunctional dendrimers, were used to provide complementary information on the dendrimer−membrane interactions. The computer-aided EPR analysis demonstrated a good agreement between the results obtained for the spin probe and spin label experiments. Both points of view suggested the partial insertion of the dendrimer surface groups into the surfactant aggregates, mainly CTAB micelles, and the occurrence of both polar and hydrophobic interactions, while dendrimer−LEC interactions involved more polar interactions between surface groups. We found out that subtle changes in the dendrimer structure greatly modified their interacting abilities and, subsequently, their anticancer activity.

【 授权许可】

Unknown