Abstract
AbstractProtease‐triggered control of functional DNA has remained unachieved, leaving a significant gap in activatable DNA biotechnology. Herein, we report the design of a protease‐activatable aptamer system that can perform molecular sensing and imaging in a tumor‐specific manner. The system is constructed by locking the structure‐switching activity of an aptamer using a rationally designed PNA–peptide–PNA triblock copolymer. Highly selective protease‐mediated cleavage of the peptide substrate results in reduced binding affinity of PNA to the aptamer module, with the subsequent recovery of its biosensing function. We demonstrated that the DNA/peptide/PNA hybrid system allows for tumor cell‐selective ATP imaging in vitro and also produces a fluorescent signal in vivo with improved tumor specificity. This work illustrates the potential of bridging the gap between functional DNA and peptides for precise biomedical applications.
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