Light-Driven Upconverting Nanoparticles-Based Nanodevice for Accurate Subcellular Dual Molecular Imaging and Combinational Tumor Therapy

The development of nanodevices for simultaneous imaging, accurate diagnosis, and efficient therapy with high spatiotemporal precision remains highly challenging. Herein, we proposed an intelligent strategy that employed the light-controlled DNAzyme probe for dual-target imaging and integrated it with upconversion nanoparticle (UCNPs)-based synergistic therapy in mitochondria. This nanosystem was composed of silica-shelled UCNPs surrounded by DNA probes and mitochondria-targeting triphenylphosphonium. The core/shell-structured UCNPs were capable of codelivering photosensitizer molecules (Ce6) and DOX. Following controlled localization and photoactivation, the engineered DNAzyme probes first visualized miRNA-21 and subsequently allowed for the imaging of human uracil/pyrimidine-free nucleic acid endonuclease 1 (APE1). Once the target was recognized, the treatment was also performed with released DOX and near-infrared (NIR) light-mediated photodynamic therapy. As a result, the all-in-one nanodevice enabled specific imaging of tumors and enhanced synergistic therapy efficacy in live biosystems with high precision both spatially and temporally. These findings are expected to drive forward research on the utilization of intelligent nanodevices in the converging realms of diagnostic and therapeutic applications.