Mitochondria‐ and Lysosomes‐Targeted Synergistic Chemo‐Photodynamic Therapy Associated with Self‐Monitoring by Dual Light‐Up Fluorescence

Abstract The current cancer therapy faces great challenges on improving the treatment efficiency and overcoming the drug resistance. To tackle these challenges, herein dual‐organelle‐targeted nanoparticles (NPs) are developed with synergistic chemo‐photodynamic therapy functions through self‐assembly of mitochondria‐targeted chemotherapeutic agent AIE‐Mito‐TPP and lysosomes‐targeted photosensitizer AlPcSNa 4 . The dual‐organelle‐targeted NPs can be quickly taken up by cancer cells through endocytosis and gradually decompose to release AIE‐Mito‐TPP and AlPcSNa 4 , which, respectively, accumulate in mitochondria and lysosomes. The AIE‐Mito‐TPP can efficiently destroy mitochondrial functions, while the AlPcSNa 4 can efficiently destroy lysosomes via reactive oxygen species generation under NIR light irradiation. The dual‐organelle‐targeted drug delivery process can also be self‐monitored by the dual light‐up fluorescence of green‐emissive AIE‐Mito‐TPP and red‐emissive AlPcSNa 4 . With A375 cells and A375‐bearing nude mice as a model, the theranostic potential of the AIE‐Mito‐TPP/AlPcSNa 4 NPs is systematically investigated both in vitro and in vivo. Under NIR light irradiation, the AIE‐Mito‐TPP/AlPcSNa 4 NPs show a remarkable cytotoxicity against A375 cells and efficiently inhibit the in vivo tumor growth. Therefore, the theranostic NPs with dual‐organelle‐targeted and synergistic chemo‐photodynamic therapy functions associated with self‐monitoring ability are expected to have promising applications in imaging‐guided precise cancer therapy.