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

摘要

As a result of inaccurate biosensing and difficult synergeticloading,it is challenging to further impel DNA amplifiers to perform therapeuticapplication. Herein, we introduce some innovative solutions. First,a smart light-driven biosensing concept based on embedding nucleicacid modules with a simple photocleavage-linker is proposed. In thissystem, the target identification component is exposed on irradiationwith ultraviolet light, thus avoiding an always-on biosensing responseduring biological delivery. Further, in addition to providing controlledspatiotemporal behavior and precise biosensing information, a metal-organicframework is used for the synergetic loading of doxorubicin in theinternal pores, whereafter a rigid DNA tetrahedron-sustained exonucleaseIII-powered biosensing system is attached to prevent drug leakageand enhance resistance to enzymatic degradation. By selecting a next-generationbreast 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 mismatchingis demonstrated. Moreover, the all-in-one DNA amplifier shows excellentbioimaging competence and good chemotherapy efficacy in live biosystems.These findings will drive research into the use of DNA amplifiersin diagnosis and therapy integrated fields.

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