Engineering Living Mitochondria with AIE Photosensitizer for Synergistic Cancer Cell Ablation

Photodynamic therapy (PDT) has been increasingly studied in cancer treatment, and several factors have been identified to limit the PDT therapeutic efficiency. Taking Bcl-2 protein as an example, its overexpressing in cancer cells could strengthen the antioxidant and antiapoptotic capability of the cells, making PDT less effective in cancer cell treatment. To address this issue, we developed an engineered living system by integrating an aggregation-induced emission photosensitizer (AIE PS) with bioactive mitochondria (Mito-AIEgen-lipid) for enhanced PDT. The AIE PS engineered mitochondria could not only change the energetic metabolism of cancer cells from aerobic glycolysis to normal oxide phosphorylation for cancer cell growth inhibition but also activate the apoptotic pathway and reduce the expression of antiapoptotic protein Bcl-2. This specific organelle-based living system holds great promise to enhance the therapeutic efficiency of PDT by integrating the advantages of synthetic organic small molecules with biological components.