Cytosolic delivery of proteins mediated by aldehyde-displaying silica nanoparticles with pH-responsive characteristics

Synthetic carriers that enable site-specific intracellular delivery of proteins are valuable in many biomedical applications. Aldehyde-displaying silica nanoparticles (MSN-aldehyde) containing lysosome activatable rhodamine-lactams were prepared for fluorescent tracking and delivery of proteins via lysosomal acidity-triggered release of proteins and “turn-on” fluorescence of doped rhodamine-lactam. The carrier-protein nanocomposites were site-specifically internalized into lysosomes of HepG2, HeLa and L929 cells where the loaded proteins, including arginase and green fluorescent protein, were released via lysosomal acidity-mediated hydrolysis of the bridging imine linkages. The released proteins efficiently escaped from lysosomes into cytosol where arginase effectively induced autophagy of the host cells. With the ease of formation of pH-labile imine linkages between MSN-aldehyde and lysine of various proteins, MSN-aldehyde would be of interest as a general vector for cytosolic delivery of proteins.