Many Birds, One Stone: A Smart Nanodevice for Ratiometric Dual-Spectrum Assay of Intracellular MicroRNA and Multimodal Synergetic Cancer Therapy

The development of a theragnostic platform integrating precise diagnosis and effective treatment is significant but still extremely challenging. Herein, an integrated smart nanodevice composed of Au@Cu2–xS@polydopamine nanoparticles (ACSPs) and fuel DNA-conjugated tetrahedral DNA nanostructures (fTDNs) was constructed, in which the ACSP nanoprobe played multiple key roles in antitumor therapy as well as in situ monitoring of microRNAs (miRNAs) in cancer cells. Regarding the analysis, the ACSP probe contained two optical properties: excellent surface-enhanced Raman scattering (SERS) enhancement and high fluorescence (FL) quenching performance. Employing the ACSPs as the high-efficiency detection substrate combined with the fTDN-assisted DNA walking nanomachines as the superior amplification strategy, a SERS-FL dual-spectrum biosensor was constructed, which achieved an ultralow background signal and excellent sensitivity with detection limits of 0.11 pM and 4.95 aM by FL and SERS, respectively. Moreover, the rapid FL imaging and precise SERS quantitative detection for miRNA in cancer cells were also achieved by dual-signal ratio strategy, improving the accuracy of diagnosis. Regarding the therapeutic application, due to the high reactive oxygen species generation ability and excellent photothermal conversion efficiency, the ACSPs can also act as an all-in-one nanoagent for multimodal collaborative tumor therapy. Significantly, both in vivo and in vitro experiments confirmed its high biological safety and strong anticancer effect, indicating its promising theragnostic applications.