Enzyme-responsive silica mesoporous supports capped with azopyridinium salts for controlled delivery applications

11 páginas, 7 figuras, 3 tablas y 2 esquemas
The preparation of a new capped silica mesoporous material, Rh-Azo-S, for on-command delivery applications in the presence of target enzymes is described. The material consists of nanometric mesoporous MCM-41-like supports loaded with Rhodamine B and capped with an azopyridine derivative. The material was designed to show “zero delivery” and to display a cargo release in the presence of reductases and esterases, which are usually present in the colon, mainly due to intestinal microflora. The opening and cargo release of Rh-Azo-S in vitro studies were assessed and seen to occur in the presence of these enzymes, whereas no delivery was noted in the presence of pepsine. Moreover, Rh-Azo-S nanoparticles were used to study controlled Rhodamine B dye delivery in intracellular media. HeLa cells were employed for testing the “non”-toxicity of nanoparticles. Moreover, delivery of the dye in these cells, through internalization and enzyme-mediated gate opening, was confirmed by confocal microscopy. Furthermore, the nanoparticles capped with the Azo group and loaded with a cytotoxic camptothecin (CPT) were also prepared (solid CPT-Azo-S) and used as delivery nanodevices in HeLa cells. When this solid was employed, the cell viability decreased significantly due to internalization of the nanoparticles and delivery of the cytotoxic agent.
We thank the Spanish Government (projects MAT2009-14564-C04, MAT2012-38429-C04-01, CTQ2007-64735-AR07 and SAF2010-15512) the Generalitat Valenciana (projects PROMETEO/2009/016 and /2010/ 005) for their support. N.M. thanks the Ministerio de Ciencia e Innovaci n for her FPU grant. A.A. and L.M. thank the Generalitat Valenciana for their Santiago Grisolia fellowships and VALI+D postdoctoral contracts.