Hydrogen as a Bio-orthogonal Trigger for Spatiotemporally Controlled Caged Prodrug Activation

The use of a p-nitrobenzyloxycarbonyl (pNZ) protecting group on the FDA-approved lung cancer drug gemcitabine affords a caged drug with very low in vitro toxicity in a human model cell line (A549). To activate this type of caged potent drug, simultaneous presence of two items is needed: platinum nanoparticles and hydrogen-containing gas mixtures. This combination may later allow a more precise and controlled local delivery of highly potent cytostatic compounds, and may eventually permit reduction of the severe side effects of such chemotherapy treatments. Hydrogen, though an unusual medical agent, is well tolerated, and here used mixtures are derived from diving (deep diving gas). Pt nanoparticles at here used concentrations may eventually be locally deposited into the lungs through minimal invasive inhalation. We demonstrate the use of hydrogen as an on/off uncaging switch and show repeated use of the Pt nanoparticles for a series of uncaging events.