This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Nano, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/nn101499d. ; The synthesis of new capped silica mesoporous nanoparticles for on-command delivery applications is described. The gate-like functional hybrid systems consisted of nanoscopic MCM-41-based materials functionalized on the pore outlets with different “saccharide” derivatives and a dye contained in the mesopores. A series of hydrolyzed starch products as saccharides were selected. The mesoporous silica nanoparticles S1, S2, and S3 containing the grafted starch derivatives Glucidex 47, Gludicex 39, and Glucidex 29 were synthesized. Additionally, for comparative purposes solid S4 containing lactose was prepared. Delivery studies in pure water in the presence of pancreatin or -D-galactosidase were carried out for S1S3 and S4, respectively. S1, S2, and especially S3 showed very low release in the absence of enzyme, but displayed cargo delivery in the presence of the corresponding enzyme. Moreover, nanoparticles of S1 were used to study the controlled release of the dye in intracellular media. Cell viability assays using HeLa and LLC-PK1 cells indicated that S1 nanoparticles were devoid of unspecific cell toxicity. The endocytosis process for S1 nanoparticle internalization in HeLa cells was confirmed, and the anchored starch was degraded by the lysosomal enzymes. Furthermore, a new mesoporous silica nanoparticle functionalized with Glucidex 47 and loaded with a cytotoxic, S1-DOX, was developed. The cell viability with S1-DOX decreased due to the internalization of the nanoparticle, enzyme-dependent opening of the saccharide molecular gate and the consequent release of the cytotoxic agent. As far as the authors know, this is the first example of enzyme-induced in-cell delivery using capped silica mesoporous nanoparticles. ; Government (Spain) MAT2009-14564-C04- 01 ; Government (Spain) MAT2009-14564-C04-04 ; Government (Spain) BIO2007-60066 ; Generalitat Valenciana PROMETEO/2009/016 ; Generalitat Valenciana PROMETEO/2010/005 ; Universitat Politècnica de València FPI grant ; MICINN FPU contract ; Bernardos Bau, A.; Mondragón Martínez, L.; Aznar, E.; Marcos Martínez, MD.; Martínez-Máñez, R.; Sancenón Galarza, F.; Soto Camino, J. (2010). Enzyme-responsive intracellular controlled release using nanometric silica mesoporous supports capped with "saccharides". ACS Nano. 4(11):6353-6368. doi:10.1021/nn101499d. ; Senia ; 6353 ; 6368 ; 4 ; 11