Biodegradable Metal–Organic Frameworks Power DNAzyme for in Vivo Temporal-Spatial Control Fluorescence Imaging of Aberrant MicroRNA and Hypoxic Tumor

MicroRNAs (miRNAs) are involved in the essential progresses of many diseases and have emerged as therapeutic and diagnostic biomarkers. The combination of miRNA aberrant expression and tumor microenvironment (TME) features holds great potential for precise tumor imaging diagnosis but has been minimally explored. Herein, we rationally design a DNA@Cu-MOF nanosystem containing copper metal–organic frameworks (Cu-MOF) and a DNAzyme-assisted signal amplification procedure for deregulated miRNA-related hypoxic tumor diagnosis. The nanoprobes comprising a signal strand block Cu-specific DNAzyme precursor and a substrate strand are assembled on the surface of the hypoxia-responsive Cu-MOF. Under TME characterized by hypoxia, the DNA@Cu-MOF nanosystem disassociates and accomplishes the release of abundant Cu2+, DNAzyme precursor, and substrate strand. Target aberrant miRNA displaces the signal strand to recover one fluorescence signal for detection. Importantly, it activates the Cu-specific DNAzyme amplification, which produces miRNA aberrant expression-dependent fluorescence signal for hypoxic tumor diagnosis. Both in vitro and in vivo experiments validate its good performance for tumor cell diagnosis. The hypoxia-driven and miRNA-binding-induced self-powered and temporal-spatial fluorescence imaging nanosystem not only provides a great tool for aberrant miRNA-related hypoxic tumor diagnosis but also is readily applied for the control and modulation of biological functions.