Near‐Infrared Light‐Activatable Spherical Nucleic Acids for Conditional Control of Protein Activity

Optical control of protein activity represents a promising strategy for precise modulation of biological processes. We report rationally designed, aptamer-based spherical nucleic acids (SNAs) capable of noninvasive and programmable regulation of target protein activity by deep-tissue-penetrable near-infrared (NIR) light. The photoresponsive SNAs are constructed by integrating activatable aptamer modules onto the surface of upconversion nanoparticles. The SNAs remain inert but can be remotely reverted by NIR light irradiation to capture the target protein and thus function as an enzyme inhibitor, while introduction of antidote DNA could further reverse their inhibition functions. Furthermore, we demonstrate the potential of the SNAs as controllable anticoagulants for the NIR light-triggered regulation of thrombin function. Ultimately, the availability of diverse aptamers would allow the design to regulate the activities of various proteins in a programmable manner.