Exploring the Interactions of Ruthenium (II) carbosilane metallodendrimers and precursors with model cell membranes through a dual spin label spin probe technique using EPR
Authors
Carloni, Riccardo; Sanz del Olmo, Natalia; Ortega Lopez, Paula; Fattori, Alberto; Gómez Ramírez, Rafael; [et al.]Identifiers
Permanent link (URI): http://hdl.handle.net/10017/46747DOI: 10.3390/biom9100540
ISSN: 2218-273X
Date
2019-09-27Bibliographic citation
Biomolecules, 2019, v. 9, n. 10, p. 540
Keywords
electron paramagnetic resonance
dendrimer
metallodendrimer
ruthenium
cell membrane
spin probe
cancer
Project
CTQ2017-86224-P (MINECO); 2017-T2/IND-5243, B2017/BMD-3733 and B2017/BMD-3703 (Comunidad de Madrid); SBPLY/17/180501/000358 (Junta de Comunidades de Castilla-la Mancha); CIBER-BBN (Instituto de Salud Carlos III); COST Action CA17140.
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Rights
Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
MDPI, 2019
Access rights
info:eu-repo/semantics/openAccess
Abstract
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.
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