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

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 AlPcSNa4. The dual-organelle-targeted NPs can be quickly taken up by cancer cells through endocytosis and gradually decompose to release AIE-Mito-TPP and AlPcSNa4, which, respectively, accumulate in mitochondria and lysosomes. The AIE-Mito-TPP can efficiently destroy mitochondrial functions, while the AlPcSNa4 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 AlPcSNa4. With A375 cells and A375-bearing nude mice as a model, the theranostic potential of the AIE-Mito-TPP/AlPcSNa4 NPs is systematically investigated both in vitro and in vivo. Under NIR light irradiation, the AIE-Mito-TPP/AlPcSNa4 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.