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

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.

Antioxidant and Antibacterial Properties of Carbosilane Dendrimers Functionalized with Polyphenolic Moieties

“…In 2016, our research group described a new family of polyphenolic carbosilane dendrimers functionalized with vanillin that showed promising antioxidant activity, as well as high potential as anticancer agents against an advanced prostate cancer cell line (PC-3) [ 9 ]. The high stability and very low hydrophilicity of the carbosilane skeleton might improve their interaction with membranes [ 13 , 14 , 15 ]. As a new goal, our research group focused its attention on three polyphenolic acids, ferulic (3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid), caffeic (3-3,4-dihydroxyphenyl)-2-propenoic acid), and gallic (3,4,5-trihydroxybenzoic acid), due to their antioxidant activity and potential for application in the biomedical field.…”

Triazine–Carbosilane Dendrimersomes Enhance Cellular Uptake and Phototoxic Activity of Rose Bengal in Basal Cell Skin Carcinoma Cells

“…Encapsulation protects a drug from degradation en route to the tumor. 22 Carbosilane dendritic architecture is versatile for designing functional systems for therapy, 46–49 imaging 50 and nanoparticle decoration. 51–53 Furthermore, the chemical structure of carbosilane dendrons containing two orthogonal functionalities favors the synthesis of amphiphilic derivatives self-organizing into micelles 54–56 or dendrimersomes.…”

Synthesis and biological and physico-chemical characterization of glycodendrimers and oligopeptides for the treatment of systemic lupus erythematosus

“…For the unlabelled glycodendrimers, a spin-probe was used to analyse the interactions among the components. After an accurate screening and on the basis of previous studies, 31,32 we selected the spin probe 4-dodecyldimethylammonium-2,2,6,6-tetramethyl-piperidine-1-oxyl bromide (termed CAT12), characterized by an amphiphilic structure, with a positively charged head and a hydrophobic chain of 12 saturated carbons. We tried several other spin probes, but CAT12 was the one providing the largest spectral differences among the various systems, thus characterizing the types and strengths of the occurring interactions.…”