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

Sauer, Anna M; Schlossbauer, Axel; Ruthardt, Nadia; Cauda, Valentina; Bein, Thomas; Bräuchle, Christoph · Nano Lett · 2010

basic_science · Level V

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Abstract

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.

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