3D DNAzyme Motor Nanodevice With Self‐Powered FRET Amplifier and Self‐Supplied H2O2 for Enhancing Human Neutrophil Elastase Profiling and Chemodynamic Therapy in Lung Tumor

Abstract The development of theragnostic nanosystems integrating FRET (fluorescence resonance energy transfer) imaging and chemodynamic therapy (CDT) for accurate diagnosis and effective treatment of lung tumors is still a big challenge. Herein, a peptide‐assembled 3D DNAzyme motor nanodevice is engineered for a self‐powered FRET amplifier profiling human neutrophil elastase (HNE) and self‐supplied H 2 O 2 enhancing CDT. The nanodevice is prepared by depositing AuNPs on ZIF‐8, in which ZIF‐8 co‐loaded the lysosomal targeting peptide‐modified copper peroxides (PCPs) and hairpins (H1, H2, and H3), AuNPs are co‐labeled by DNAzyme‐peptide (DP) conjugate and H3. In the tumor micro‐environment, HNE driven 3D DNAzyme walker followed by an exponential amplification constructed by a synergistic cross‐activation between hybridization chain reaction and DNAzyme, generating a self‐powered FRET amplifier. The FRET amplifier specifically measures HNE with a sensitivity of 0.026 pM, and successfully images exogenous HNE in living cells and monitors HNE in mouse models. Moreover, the PCPs can target lysosomes, reducing lysosome escape. The self‐supplying H 2 O 2 undertaken by PCPs improves the Cu (II)‐catalyzed Fenton‐like reaction, effectively causing cell apoptosis to inhibit tumor growth. Significantly, the nanodevice successfully screens inhibitors and discriminates the HNE level in normal and lung cancer tissues, suggesting that the nanodevice provides an effective tool for the diagnosis and treatment of lung tumors.