AS1411 derivatives as carriers of G-quadruplex ligands for cervical cancer cells

Publication date: Available online 10 July 2019Source: International Journal of PharmaceuticsAuthor(s): Joana Figueiredo, Jéssica Lopes-Nunes, Josué Carvalho, Francisca Antunes, Márcia Ribeiro, Maria Paula Cabral Campello, António Paulo, Artur Paiva, Gilmar F. Salgado, João A. Queiroz, Jean-Louis Mergny, Carla CruzAbstractNucleic acid aptamers can specifically bind to target molecules on the cell membrane that mediate their entrance into the cells. Their small size, high binding affinity, specificity, good biocompatibility, stability and low immunogenicity make them ideal drug delivery systems for cancer therapy. These biopharmaceuticals have potential for the delivery of anticancer compounds to diseased tissues, increasing their effectiveness while mitigating the off-target toxicity towards healthy cells. Herein, we have studied two quadruplex-forming DNA sequences derived from the nucleolin-targeted aptamer AS1411 as supramolecular carriers for the cancer-selective delivery of acridine orange derivatives (C3, C5 and C8) in cervical cancer cells.The devised delivery strategy relied on the non-covalent association of the acridine derivatives and the G-quadruplex (G4) structures. This association is done with a high binding strength, as suggested by the obtained KD values in the 10-6 – 10-7 M range, leading to the thermal stabilization of the G4 structures, particularly for C8. The stability of the resulting supramolecular conjugates was evaluated in fetal bovine serum,...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research