Near‐Infrared Photoaccelerated MicroRNA Response for Image‐Guided Photodynamic‐Chemodynamic Synergistic Cancer Therapy via Nanoprobe Programmed Disassembly

Abstract Accurate detection of disease biomarkers in situ is essential for early cancer diagnosis and treatment. Herein, we delicately designed a multifunctional nanoprobe, GNP@Pt‐QDs/AIE, for the imaging of miRNA biomarkers in living cells and tissues and image‐guided synergistic cancer therapy. Using chimeric phosphodiester‐phosphorothioate DNA and dual‐thiol grouped aggregation‐induced emission (AIE) photosensitizer as co‐ligands, monovalent DNA‐modified quantum dot (QD) is synthesized with strong photosensitization via efficient energy transfer between QD and the surface‐coordinated photosensitizers. Through DNA‐programmed assembly with a peroxidase‐mimetic platinum‐shelled gold nanoparticle (GNP@Pt), a core‐satellite GNP@Pt‐QDs/AIE nanoprobe is constructed that completely quenched both fluorescence and reactive oxygen species (ROS). Upon response to miRNA target, QDs are programmatically disassembled from the nanoprobes, leading to amplified fluorescence and photodynamic activity. Concurrently, the steric hindrance of the platinum shell is relieved with oxygen‐independent chemodynamic activity restored. More significantly, the mild photothermal effect under near‐infrared (NIR) irradiation can accelerate the disassembly to fast activate fluorescence and ROS output. Excellent performances in miRNA‐21 target imaging and chemodynamic‐photodynamic synergistic anticancer therapy are achieved in vitro and in vivo with negligible cytotoxicity. This NIR‐photoaccelerable nanoprobe, capable of imaging miRNA biomarkers in situ and synergizing chemodynamic‐photodynamic therapy, offers great potential for the early diagnosis and treatment of malignancies.