Light-triggered inactivation of enzymes with photothermal nanoheaters

Enzymes are crucial for the cell metabolism and in industrial applications such as the manufacture of biosensors and medicines. A method for inactivating enzymes non-invasively and on demand could reveal the role of a biocatalyst in a particular cell function and enable fine-tuning the therapeutic dose of enzyme-based drugs. In this manuscript we introduce a universal method for inactivating enzymes with light. It consists of attaching the enzymes to photothermal nanoheaters (gold nanorods). Upon irradiation with light resonant with their LSPR the plasmonic nanoparticles generate heat, which denatures the enzymes. The resulting increase in temperature is highest in the vicinity of the nanoheaters, which allows the localized inactivation of nanorod-bound enzymes without damaging other proteins or cell membranes present in the same solution. Here we demonstrate this concept by selectively turning off an enzyme cascade via the selective inactivation of one of its components. We also prove that the target enzyme can be inactivated without unduly damaging cells under controlled irradiation conditions. The results shown here pave the way for using the proposed methodology to discern the role of target enzymes in intracellular signaling pathways.