Peptide Nucleic Acid (PNA)-Guided Peptide Engineering of an Aptamer Sensor for Protease-Triggered Molecular Imaging.
Protease-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.
['Xiang|Zhichu|Z|', 'Zhao|Jian|J|', 'Yi|Deyu|D|', 'Di|Zhenghan|Z|', 'Li|Lele|L|0000-0001-8593-9292']
D000818:Animals D052157:Aptamers, Nucleotide D015374:Biosensing Techniques D002401:Cathepsin B D006367:HeLa Cells D006801:Humans D051379:Mice D008819:Mice, Nude D018613:Microscopy, Confocal D009369:Neoplasms D061848:Optical Imaging D010447:Peptide Hydrolases D020135:Peptide Nucleic Acids D015202:Protein Engineering D014183:Transplantation, Heterologous
peptide nucleic acids molecular imaging DNA aptamers activatable biosensors proteases