Light-Driven and Metal–Organic Framework Synergetic Loaded DNA Tetrahedral Amplifier for Exonuclease III-Powered All-in-One Biosensing and Chemotherapy in Live Biosystems

As a result of inaccurate biosensing and difficult synergetic loading, it is challenging to further impel DNA amplifiers to perform therapeutic application. Herein, we introduce some innovative solutions. First, a smart light-driven biosensing concept based on embedding nucleic acid modules with a simple photocleavage-linker is proposed. In this system, the target identification component is exposed on irradiation with ultraviolet light, thus avoiding an always-on biosensing response during biological delivery. Further, in addition to providing controlled spatiotemporal behavior and precise biosensing information, a metal–organic framework is used for the synergetic loading of doxorubicin in the internal pores, whereafter a rigid DNA tetrahedron-sustained exonuclease III-powered biosensing system is attached to prevent drug leakage and enhance resistance to enzymatic degradation. By selecting a next-generation breast cancer correlative noncoding microRNA biomarker (miRNA-21) as a model low-abundance analyte, a highly sensitive in vitro detection ability even allowing to distinguish single-base mismatching is demonstrated. Moreover, the all-in-one DNA amplifier shows excellent bioimaging competence and good chemotherapy efficacy in live biosystems. These findings will drive research into the use of DNA amplifiers in diagnosis and therapy integrated fields.