To establish a new method for tracking the interaction of nanoparticles with chemical cleaving agents, we exploited the optical effects caused by attaching 5–10 nm gold nanoparticles with molecular linkers to large mesoporous silica nanoparticles (MSN). At low levels of gold loading onto MSN, the optical spectra resemble colloidal suspensions of gold. As the gold is removed, by cleaving agents, the MSN revert to the optical spectra typical of bare silica. Time-lapse images of gold-capped MSN stationed in microchannels reveal that the rate of gold release is dependent on the concentration of the cleaving agent. The uncapping process was also monitored successfully for MSN endocytosed by A549 cancer cells, which produce the cleaving agent glutathione. These experiments demonstrate that the optical properties of MSN can be used to directly monitor cleaving kinetics, even in complex cellular settings.