The Construction Of Cationic AIE Theranostic Probes And Their Anticancer And Antimicrobial Applications

Cancer and pathogenic infection are closely related and are the most serious health threats,and they are closely related.On one hand,pathogenic infection can induce cancer;on the other hand,advanced cancer patients with weakened immunity are more susceptible to pathogenic infection.Currently,multiple anticancer drugs and antimicrobial agents are simultaneously used in clinic to achieve targeted treatment.However,the multiple use of different drugs significantly increases potential risks and adverse effects（such as drug resistance）.In addition,in order to precisely kill cancer cells or pathogens,theranostic molecular probe with imaging function is urgently needed.The conventional fluorophores suffer from aggregation-caused quenching（ACQ）drawbacks after being enriched in the cancer cell organelles or pathogens.In order to overcome the drawbacks,more attention has been paid to the aggregation-induced emission（AIE）probe with diagnosis and treatment function.AIE probes are not only suitable for high spatiotemporal resolution imaging of subcellular organelles and pathogens,but also can kill them effectively.However,in view of the urgent need in clinic,it is rarely reported on AIE probes which can simultaneously achieve the imaging and treatment of cancer cells,bacteria and fungi.To realize imaging-guided precise treatment of cancer,bacteria and fungi,and in situ monitor the treatment process,we designed and developed a series of AIE probes,which can achieve the precise killing of cancer cells,bacteria and fungi.The specific research contents are as follows:（1）Cancer chemotherapy faces the challenge of drug resistance,because chemotherapeutic drugs are excreted from cancer cells by the cell membrane efflux pump.Organelle-targeted drugs can be selectively accumulated in subcellular compartments to inhibit drug efflux and improve the killing efficiency of cancer cells.In this chapter,we designed and synthesized mitochondria-and lysosomes-targeted theranostic nanoprobe AIE-Mito-TPP/Al Pc SNa₄ NPs through self-assembly of mitochondria-targeted AIE molecule AIE-Mito-TPP and lysosomes-targeted photosensitizer Al Pc SNa4.The intracellular release process of AIE-Mito-TPP/Al Pc SNa₄ NPs could be monitored in situ by the dual light-up fluorescence.At the same time,the mitochondria-targeted AIE-Mito-TPP could act as a chemotherapeutic agent to destroy mitochondrial function,while Al Pc SNa₄ could act as a photodynamic agent to efficiently destroy lysosomes.The dual-organelle-targeted and synergistic chemo-photodynamic therapy could efficiently kill cancer cells in vitro and inhibit tumor growth in vivo.（2）Pathogenic infection is closely related with the initiation and progression of cancer,and cancer patients with weakened immunity are more susceptible to pathogenic infection.Based on the cationic AIE-Mito-TPP probe,we further found that AIE-Mito-TPP could light up and effectively kill bacteria and fungi.This is due to the positive charge and hydrophobic characteristic of AIE-Mito-TPP probe,which has a good binding capacity and excellent destruction efficacy towards the negatively charged bacterial membrane,while its excellent antifungal activity could be also achieved by efficiently destroy mitochondrial structure and function.Further,we found that the AIE-Mito-TPP probe could realize the sequential imaging and killing of bacteria and cancer cells.（3）Chemotherapy faces drug resistance,while photosensitizers-based photodynamic therapy（PDT）can produce reactive oxygen species（ROS）under specific light irradiation to destroy their physical and chemical structure,which is not easy to produce drug resistance.However,the photodynamic activity of the traditional photosensitizer decreases sharply in the aggregation state.In order to overcome this defect,we designed and synthesized AIE-active photosensitizer TPATHP with high photodynamic activity in the aggregation state.The AIE photosensitizer could not only realize the targeted fluorescence imaging of cell membrane and mitochondria of cancer cells,but also realize the wash-free imaging of Gram-positive bacteria,Gram-negative bacteria and fungi.Under the white light irradiation,TPATHP probe could efficiently generated ROS,which could not only effectively kill cancer cells through the destruction of the structure and function of cell membrane and mitochondria,but also effectively kill bacteria and fungi through the destruction of bacterial membrane and fungal mitochondria.In addition,the TPATHP probe could real-time regulate the treatment process of targeting cell membrane and mitochondria by monitoring in situ the morphological changes of cell membrane and mitochondria via fluorescence imaging.It is worth noting that the AIE photosensitizer TPATHP had low dark toxicity and could selectively kill cancer cells,bacteria and fungi by controlling light irradiation.Finally,an outlook is provided for the theranostic potential of AIE probes in treatment of cancer and pathogens.