RNA-cleaving DNAzymes are widely applied as sensors for detecting metal ions in environmental samples owing to their high sensitivity and selectivity, but their use for sensing biological metal ions in live cells is challenging because constitutive sensors fail to report the spatiotemporal heterogeneity of biological processes. Photocaged DNAzymes can be activated by light for sensing purposes that need spatial and temporal resolution. Studying complex biological processes requires logic photocontrol, but unfortunately all the literature-reported photocaged DNAzymes working in live cells cannot be selectively controlled by light irradiation at different wavelengths. In this work, we developed photocaged DNAzymes responsive to UV and visible light using a general synthetic method based on phosphorothioate chemistry. Taking the Zn2+-dependent DNAzyme sensor as a model, we achieved wavelength-selective activation of photocaged DNAzymes in live human cells by UV and visible light, laying the groundwork for the logic activation of DNAzyme-based sensors in biological systems.
© 2021 The Authors. Published by American Chemical Society.