DNA‐Based Biosensors for Imaging of Subcellular Enzymatic Activity

Abstract

As one kind of the most important biomolecules, enzymes participate in nearly all biochemical reactions. Dysregulation of enzymes' spatial distributions and activities is often associated with many diseases. In situ imaging of enzymatic activity at the subcellular level is extremely challenging due to the lack of spatiotemporal precision of sensor probes. In this concept, we introduce several recent works in which DNA-based biosensors with controllable localization ability were constructed for imaging of specific enzymatic activities and dynamics in a subcellular compartment of interest. These DNA-based biosensors are classified into two types, in which DNA molecules serve as a subcellular targeting scaffold and an enzyme responsive sensing unit, respectively. We highlight the working principles of these DNA-based biosensors and briefly introduce their biological applications. Finally, we discuss current limitations and future opportunities in this emerging field.

An Enzymatically Activated and Catalytic Hairpin Assembly-Driven Intelligent AND-Gated DNA Network for Tumor Molecular Imaging

“…activation. ,,− The near-infrared (NIR) light-activated signal amplification strategies have been previously reported for exogenous activation. However, despite exogenously activated tumor-specific imaging has been widely used, there still exist substantial limitations of not being able to tumor site, which currently hinders their clinical applicability. − In contrast, endogenous activation offers an alternative approach to achieve tumor-specific imaging with enhanced efficiency. However, due to the complex tumor microenvironment and the instability of catalytic groups, the current endogenous activation-based approaches still have limitations in terms of achieving tumor-specific imaging. ,,− Preliminary investigations showed that apurinic/apyrimidinic endonuclease 1 (APE1), a pivotal enzyme that mediates the hydrolysis of apurinic/apyrimidinic (AP) sites, predominantly localizes to the nucleus in normal cells but exhibits enhanced expression in both the cytosolic and nuclear compartments of the cancer cell.…”