NAzyme activity surface plasmon resonance sensors include a first DNA probe that is covalently connected to a sensing surface, and a second DNA probe that is covalently connected to a nanoparticle or a nanoparticle cluster. The first DNA probe and the second DNA probe are ligated together to provide a selected single strand DNA probe connected to the sensing surface and the nanoparticle. The single strand DNA probe includes a ligation zone within a selected NAzyme substrate. The sensor measures DNAzyme activity by NAzyme binding at the NAzyme substrate and cleavage at the ligation zone. Fiber optic surface plasmon resonance sensor tips are adapted to measure activity of a NAzyme when the NAzyme substrate is recognized by the selected NAzyme through hybridization and the metallic nanoparticle is released from the sensor by cleavage of the single strand DNA at the ligation zone by the selected NAzyme.