Enzymatically Controlled Nanoflares for Specific Molecular Recognition and Biosensing

In situ sensing of physiological and pathological species in cancer cells is of great importance to unravel their molecular and cellular processes. However, the biosensing with conventional probes is often limited by the undesired on-target off-tumor interference. Here, we report a novel strategy to design enzymatically controlled nanoflares for sensing and imaging molecular targets in tumor cells. The triggerable nanoflare was designed via rational engineering of structure-switching aptamers with the incorporation of an enzyme-activatable site and further conjugation on gold nanoparticles. The nanoflare sensors did not respond to target molecules in normal cells, but they could be catalytically activated by specific enzymes in cancer cells, thereby enabling cancer-specific sensing and imaging in vitro and in vivo with improved tumor specificity. Considering that diverse aptamers were selected, we expect that this strategy would facilitate the precise detection of a broad range of targets in tumors and may promote the development of smart probes for cancer diagnosis.