Royal Society of ChemistryCandel Busquets, I.; Aznar Gimeno, E.; Mondragón Martínez, L.; Martínez Mañez, R.; Sancenón Galarza, F.; Marcos Martínez, MD.; Amoros Del Toro, PJ.... (2012). Amidaseresponsive controlled release of antitumoral drug into intracellular media using gluconamide-capped mesoporous silica nanoparticles. Nanoscale. 4 (22) TMCM-41 silica nanoparticles were used as inorganic scaffolding to prepare a nanoscopic-capped hybrid material S1, which was able to release an entrapped cargo in the presence of certain enzymes, whereas in the absence of enzyme, a zero release system was obtained. S1 was prepared by loading nanoparticles 10 with safranine O dye and was then capped with a gluconamide derivative. In the absence of enzyme, the release of the dye from the aqueous suspensions of S1 was inhibited as a result of the steric hindrance imposed by the bulky gluconamide derivative, the polymerized gluconamide layer and the formation of a dense hydrogen-bonded network around the pore outlets. Upon the addition of amidase and pronase enzymes, delivery of safranine O dye was observed due to the enzymatic hydrolysis of the amide bond in 15 the anchored gluconamide derivative. S1 nanoparticles were not toxic for cells, as demonstrated by cell viability assays using HeLa and MCF-7 cell lines, and were associated with lysosomes, as shown by confocal microscopy. Finally, the S1-CPT material loaded with the cytotoxic drug camptothecin and capped with the gluconamide derivative was prepared. The HeLa cells treated with S1-CPTunderwent cell death as a result of material internalization, and of the subsequent cellular enzyme-mediated 20 hydrolysis and aperture of the molecular gate, which induced the release of the camptothecin cargo.

A hybrid nanoscopic capped mesoporous material, that is selectively opened in the presence of nerve agent simulants, has been prepared and used as a probe for the chromo-fluorogenic detection of these chemicals.