Cationic poly(ester amide) dendrimers: alluring materials for biomedical applications

Novel cationic poly(ester amide) dendrimers have been synthesized by copper(i) azide-alkyne cycloaddition (CuAAC) of a tripropargylamine core and azide-terminated dendrons, in turn prepared by iterative amide coupling of the new monomer 2,2′-bis(glycyloxymethyl)propionic acid (bis-GMPA). The alternation of ester and amide groups provided a dendritic scaffold that was totally biocompatible and degradable in aqueous media at physiological and acidic pH. The tripodal dendrimers naturally formed rounded aggregates with a drug that exhibited low water solubility, camptothecin, thus improving its cell viability and anti-Hepatitis C virus (anti-HCV) activity. The presence of numerous peripheral cationic groups enabled these dendrimers to form dendriplexes with both pDNA and siRNA and they showed effective in vitro siRNA transfection in tumoral and non-tumoral cell lines.This work was financially supported by the MINECO-FEDER funds (under the projects CTQ2015-70174-P and MAT2015-66208-C3-1-P), the Miguel Servet Program from the Instituto de la Salud Carlos III (CPII13/00017 to O.A.), Instituto de Salud Carlos III and European Union (ERDF/ESF, ‘‘Investing in your future’’) (PI15/00663) and the Gobierno de Aragón-FSE (E04 and B01 research groups). Centro de Investigacion Biomédica en Red en Enfermedades Hepaticas y Digestivas (CIBERehd); and Asociación Española de Gastroenterologia (AEG). A. L. and R. C.-G. thank the MECD for their FPU grants (FPU12/05210 and FPU13/3870). R. G.-P. and R. C.-G. thank the DGA for their EPIF grants.Peer Reviewe