Cascaded photoinduced drug delivery to cells from multifunctional core-shell mesoporous silica.

Different bioactive molecules are released into living cells from lipid-covered mesoporous silica nanoparticles. The release is triggered by light, as the particles feature covalently attached photosensitizers as membrane-opening agents. It is demonstrated that the particles achieve endosomal escape and that they release their cargo into the cytosol.

Role of endosomal escape for disulfide-based drug delivery from colloidal mesoporous silica evaluated by live-cell imaging.

Redox-driven intracellular disulfide-cleavage is a promising strategy to achieve stimuli-responsive and controlled drug release. We synthesized colloidal mesoporous silica (CMS) nanoparticles with ATTO633-labeled cysteine linked to the inner particle core via disulfide-bridges and characterized their cysteine release behavior after internalization into HuH7 cells by high-resolution fluorescence microscopy. Our study revealed that endosomal escape is a bottleneck for disulfide-linkage based drug release. Photochemical opening of the endosome leads to successful delivery of fluorescently labeled cysteine to the cytosol.

Multiple core-shell functionalized colloidal mesoporous silica nanoparticles.

The selective functionalization of the inner and outer surfaces of colloidal mesoporous silica (CMS) nanoparticles with different trialkoxysilanes, following a newly developed delayed co-condensation approach, results in bifunctional CMS. Complementary CMS nanoparticles were prepared with two different functional groups located either on the outer shell or in the inner core of the particle. The identification and localization of the functional groups was achieved by means of different techniques including zeta potential, nitrogen sorption measurements, and fluorescence spectroscopy. This last technique was applied to fluorescein isothiocyanate (FITC)-labeled CMS featuring aminopropyl functional groups on the periphery or the internal pore surface of the particles. Fluorescence quenching experiments were carried out with dodecanethiolate-stabilized gold nanoparticles having a diameter greater than the pore size of the CMS. It could be shown that fluorescence quenching occurs only when the FITC is positioned on the outer surface of the CMS nanoparticles, whereas no quenching was observed for FITC located in the inner core of the nanoparticle. These results clearly confirm the controlled localization of the aminopropyl groups in the nanometer space of the CMS particles. Our approach thus offers the opportunity to synthesize, in a novel multistep co-condensation strategy, various bifunctional mesoporous nanoparticles with controlled localization of different functional groups in the inner core or on the outer shell of the nanoparticle.

Biotin-avidin as a protease-responsive cap system for controlled guest release from colloidal mesoporous silica.

Tell your guests when it's time to go: When avidin caps are attached to biotinylated colloidal mesoporous silica, the four subunits of the protein avidin can each bind to a biotin moiety attached to the surface (see picture). The resulting material is a promising candidate for the design of smart detergents or drug-delivery systems. The caps can be opened to release guest molecules by controlled enzymatic hydrolysis of the protein.

Click chemistry for high-density biofunctionalization of mesoporous silica.

The applicability of click chemistry for high-density functionalization of mesoporous silica is demonstrated. The mild conditions of the copper(I)-catalyzed Huisgen reaction allow for a surface functionalization with intact biomolecules. The high covalent enzyme functionalization density under simultaneous retention of enzyme activity and the absence of leaching demonstrate the promising potential of this approach.