Nucleic Acid-to-Small Molecule Converter through Amplified Hairpin DNA Circuits

Angew Chem Int Ed Engl. 2023 Sep 13:e202306587. doi: 10.1002/anie.202306587. Online ahead of print.ABSTRACTMany microRNAs (miRNAs) are characteristically found in cancer cells, making miRNAs promising marker biomolecules for cancer diagnosis and therapeutics. However, it is challenging to use miRNA as a cancer signature because it is difficult to convert the nucleic acid sequence information into molecular functionality. To address this challenge, we realize nucleic acid-to-small molecule converters using hairpin DNA circuits. Harnessing a Staudinger reduction as a trigger for the conversion, we constructed hybridization chain reaction (HCR) and catalytic hairpin assembly (CHA) circuits that respond to oncogenic miR-21. Fluorophore and dye molecules were released in response to miR-21 through the HCR, providing fluorogenic and chromogenic readouts. Selective cytotoxicity in miR-21-abundant cells was realized by the CHA to release the anticancer drug SN-38. This would be the first example of selective activation of a small-molecule prodrug triggered by oncogenic miRNA in human living cells.PMID:37704581 | DOI:10.1002/anie.202306587
Source: Angewandte Chemie - Category: Chemistry Authors: Source Type: research