Exploring the Influence of Spacers in EDTA-β-Cyclodextrin Dendrimers: Physicochemical Properties and In Vitro Biological Behavior

探索间隔基对 EDTA-β-环糊精树枝状聚合物物理化学性质和体外生物行为的影响

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作者:Israel González-Méndez, Kendra Sorroza-Martínez, Ignacio González-Sánchez, Jesús Gracia-Mora, María Josefa Bernad-Bernad, Marco Cerbón, Ernesto Rivera, Anatoly K Yatsimirsky

Abstract

The synthesis of a new family of ethylenediaminetetraacetic acid (EDTA) core dimers and G0 dendrimers end-capped with two and four β-cyclodextrin (βCD) moieties was performed by click-chemistry conjugation, varying the spacers attached to the core. The structure analyses were achieved in DMSO-d6 and the self-inclusion process was studied in D2O by 1H-NMR spectroscopy for all platforms. It was demonstrated that the interaction with adamantane carboxylic acid (AdCOOH) results in a guest-induced shift of the self-inclusion effect, demonstrating the full host ability of the βCD units in these new platforms without any influence of the spacer. The results of the quantitative size and water solubility measurements demonstrated the equivalence between the novel EDTA-βCD platforms and the classical PAMAM-βCD dendrimer. Finally, we determined the toxicity for all EDTA-βCD platforms in four different cell lines: two human breast cancer cells (MCF-7 and MDA-MB-231), human cervical adenocarcinoma cancer cells (HeLa), and human lung adenocarcinoma cells (SK-LU-1). The new EDTA-βCD carriers did not present any cytotoxicity in the tested cell lines, which showed that these new classes of platforms are promising candidates for drug delivery.

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