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.
Sauer
Anna M
AM
Department of Chemistry and Center for Nanoscience, University of Munich LMU, Butenandtstrasse 11, Gerhardt-Ertl-Building, 81377 Munich, Germany.
Schlossbauer
Axel
A
Ruthardt
Nadia
N
Cauda
Valentina
V
Bein
Thomas
T
Bräuchle
Christoph
C
D003102:Colloids; D004220:Disulfides / Q000737:chemistry*; D004337:Drug Carriers; D011992:Endosomes; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D012822:Silicon Dioxide / Q000737:chemistry*; D013059:Spectrum Analysis, Raman
D003102:Colloids; D004220:Disulfides; D004337:Drug Carriers; D012822:Silicon Dioxide