Intracellular ATP is an emerging biomarker for cancer early diagnosis because it is a key messenger for regulating the proliferation and migration of cancer cells.However,the conventional ATP biosensing strat-egy is o...Intracellular ATP is an emerging biomarker for cancer early diagnosis because it is a key messenger for regulating the proliferation and migration of cancer cells.However,the conventional ATP biosensing strat-egy is often limited by the undesired on-target off-tumor interference.Here,we reported a novel strategy to design enzymatically controlled DNA tetrahedron nanoprobes(En-DT)for biosensing and imaging ATP in tumor cells.The En-DT was designed via rational engineering of structure-switching aptamers with the incorporation of an enzyme-activatable site and further conjugation on the DNA tetrahedron.The En-DT could be catalytically activated by apurinic/apyrimidinic endonuclease 1(APE1)in cancer cells,but they did not respond to ATP in normal cells,thereby enabling cancer-specific ATP biosensing and imaging in vitro and in vivo with improved tumor specificity.This strategy would facilitate the precise detection of a broad range of biomarker in tumors and may promote the development of smart probes for cancer diagnosis.展开更多
基金supported by the National Natural Science Foundation of China(Nos.21877030,21735002,21778016).
文摘Intracellular ATP is an emerging biomarker for cancer early diagnosis because it is a key messenger for regulating the proliferation and migration of cancer cells.However,the conventional ATP biosensing strat-egy is often limited by the undesired on-target off-tumor interference.Here,we reported a novel strategy to design enzymatically controlled DNA tetrahedron nanoprobes(En-DT)for biosensing and imaging ATP in tumor cells.The En-DT was designed via rational engineering of structure-switching aptamers with the incorporation of an enzyme-activatable site and further conjugation on the DNA tetrahedron.The En-DT could be catalytically activated by apurinic/apyrimidinic endonuclease 1(APE1)in cancer cells,but they did not respond to ATP in normal cells,thereby enabling cancer-specific ATP biosensing and imaging in vitro and in vivo with improved tumor specificity.This strategy would facilitate the precise detection of a broad range of biomarker in tumors and may promote the development of smart probes for cancer diagnosis.