Triple-stimuli (protease/redox/pH) sensitive porous silica nanocarriers for drug delivery

For the purpose of reducing the adverse effect of antitumor drugs, a novel type of protease/redox/pH stimuli-responsive fluorescent porous silica (pSiO 2 ) nanocarrier was designed. In this system, oxidized glutathione (GSSG), a kind of peptide with disulfide linkage, was grafted onto the pSiO 2 nanospheres (NSs) via amido bonds. After that, acid-decomposable, luminescent ZnO quantum dots (QDs) were introduced to seal the nanopores of pSiO 2 NSs via covalent attachment. The ZnO QDs behave as a dual-purpose entity that not only act as a fluorescence probe for drug-release monitoring but also play the role of gatekeeper that controls the drug release. The obtained ZnO-gated pSiO 2 -GSSG NSs delivery system would achieve minimized premature release under a physiological environment. The controlled release of the drug from the ZnO-gated delivery system was realized by the acidic dissolution of ZnO QDs, reduction of disulfide bonds and cleavage of the amino bonds, leading to ZnO falling off from the surface of pSiO 2 NSs. The constructed ZnO-gated pSiO 2 -GSSG NSs delivery system has promising applications in site-specific drug release for tumor chemotherapy.