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Artemisinin and AIEgen Conjugate for Mitochondria-Targeted and Image-Guided Chemo- and Photodynamic Cancer Cell Ablation.

Cell organelle targeting is a promising approach for cancer therapy. We herein report a light-up probe (tetraphenylethenethiophene (TPETH)-Mito-1ART) to co-deliver artemisinin (ART) and an aggregation-induced emission (AIE) photosensitizer to cancer cell mitochondria for image-guided combination cancer cell ablation. This probe contains a TPETH core, two mitochondria targeting arms with ART on one arm, which show high specificity toward cancer cells over normal ones, predominant accumulation, and fluorescence turn-on in mitochondria. The fresh heme produced in mitochondria quickly activates ART, and the direct generation of reactive oxygen species at mitochondria promotes photodynamic therapy (PDT) performance. The incorporation of ART and PDT leads to a largely improved cancer cell ablation efficacy with a synergistic effect, which could quickly depolarize mitochondrial membrane and largely reduce cancer migration activity. This co-delivery strategy provides great potentials for subcellular organelle-targeted and image-guided combination cancer cell ablation.

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