Versatile and programmable dual-mode logic gold nanoflares for intracellular correlated DNA repair enzymes imaging

In situ monitoring of correlated DNA repair enzyme activities in living cells is crucial for clinical and biomedical research. Here, we introduce a versatile, programmable dual-mode logic gold nanoflares strategy for OR/AND gate logic imaging the activity of apurinic/apyrimidinic endonuclease 1 (APE1) and flap endonuclease 1 (FEN1) within cells. The logic gold nanoflares were designed via conjugating enzyme-activatable sites modified branched double-stranded DNA structures to gold nanoparticles. These meticulously engineered nanoflares specifically respond to APE1 and FEN1 in living cells through logic biocomputing, emitting a fluorescent signal that allows for the sensitive monitor of APE1 and FEN1 activities. In vitro experiments demonstrate that the nanoflares are highly biocompatible and can make effectively and sensitively judgments on the two enzyme targets across various cancer cell lines. This OR/AND dual-mode logic gold nanoflare strategy offers a straightforward tool for the comprehensive analysis of multiple DNA repair enzymes, presenting promising applications in disease diagnosis, drug efficacy evaluation, and programmable therapeutics.