An Intelligent Laser‐Free Photodynamic Therapy Based on Endogenous miRNA‐Amplified CRET Nanoplatform

Laser‐free photodynamic therapy (PDT) is a promising noninvasive therapeutic modality for deep‐seated tumor, yet is constrained by low efficiency due to the limited stimulation strategies. Herein, a novel miRNA‐responsive laser‐free PDT was developed through metal‐organic frameworks (MOFs)‐mediated chemiluminescence resonance energy transfer (CRET) nanoplatform. The photosensitizer chlorin e6 (Ce6)‐loaded MOFs were functionalized with hairpin nucleic acids for sensitive responsiveness of tumor biomarker miRNA through catalytic hairpin assembly (CHA), which enabled the amplified assembly of horseradish peroxidase (HRP)‐mimicking hemin/G‐quadruplex DNAzyme on MOFs. Simultaneously, the on‐MOF assembled DNAzymes efficiently catalyzed chemiluminescence reaction to stimulate adjacent Ce6 in the presence of luminol and H2O2, thus allowing the CRET‐mediated Ce6 luminescence and reactive oxygen species (ROS) generation for self‐illuminating PDT. The CRET nanoplatform achieved significant malignant cell apoptosis and tumor inhibition effects without external laser irradiation. It is envisioned that the miRNA‐amplified CRET nanoplatform might be a selective and highly efficient antitumor nanomedicine for precise theranostic. Tumor biomarker‐responsive theranostic holds great promise for precise medicine. Herein, a miRNA‐amplified chemiluminescence resonance energy transfer (CRET) nanoplatform was constructed for tumor‐specific laser‐free photodynamic therapy. It exhibited prominent on‐demand in vivo tumor inhibition effects, indicating an intelligent medicine.