Detalle Publicación

ARTÍCULO
Click Synthesis of Size- and Shape-Tunable Star Polymers with Functional Macrocyclic Cores for Synergistic DNA Complexation and Delivery
Autores: Carbajo Gordillo, A.I. ; Jimenez Blanco, J. L. ; Benito, J. M. ; Lana Vega, Hugo; Marcelo, G.; Di Giorgio, C.; Przybylski, C.; Hinou, H.; Cena, V.; Ortiz Mellet, C.; Mendicuti, F.; Tros de Ilarduya Apaolaza, María de la Concepción (Autor de correspondencia); Garcia Fernandez, J. M. (Autor de correspondencia)
Título de la revista: BIOMACROMOLECULES
ISSN: 1525-7797
Volumen: 21
Número: 12
Páginas: 5173 - 5188
Fecha de publicación: 2020
Lugar: WOS
Resumen:
The architectural perfection and multivalency of dendrimers have made them useful for biodelivery via peripheral functionalization and the adjustment of dendrimer generations. Modulation of the core-forming and internal matrix-forming structures offers virtually unlimited opportunities for further optimization, but only in a few cases this has been made compatible with strict diastereomeric purity over molecularly diverse series, low toxicity, and limited synthetic effort. Fully regular star polymers built on biocompatible macrocyclic platforms, such as hyperbranched cyclodextrins, offer advantages in terms of facile synthesis and flexible compositions, but core elaboration in terms of shape and function becomes problematic. Here we report the synthesis and characterization of star polymers consisting of functional trehalose-based macrocyclic cores (cyclotrehalans, CTs) and aminothiourea dendron arms, which can be efficiently synthesized from sequential click reactions of orthogonal monomers, display no cytotoxicity, and efficiently complex and deliver plasmid DNA in vitro and in vivo. When compared with some commercial cationic dendrimers or polymers, the new CT-scaffolded star polymers show better transfection efficiencies in several cell lines and structure-dependent cell selectivity patterns. Notably, the CT core could be predefined to exert Zn(II) complexing or molecular inclusion capabilities, which has been exploited to synergistically boost cell transfection by orders of magnitude and modulate the organ tropism in vivo.