Study On Photodynamic Anticancer And Antibacterial Activity Of Anionic-π AIE Photosensitizer

Photodynamic therapy（PDT）has attracted much attention in the field of anticancer and antibacterial therapy because of its advantages of low toxicity,noninvasive,and difficult to produce drug resistance.However,traditional photosensitizers suffer a lot from aggregation-caused quenching（ACQ）effect,leading to quenched reactive oxygen species（ROS）generation capability after they accumulated in diseased tissues,which seriously diminished the PDT effect.Different from the traditional ACQ photosensitizer,the aggregation induced luminescence（AIE）photosensitizer has improved the fluorescence and reactive oxygen species（ROS）production in the aggregate state,which is very conducive to the application of PDT.However,most AIE photosensitizers are hydrophobic,which leads to unsatisfactory tumor treatment effect.The introduction of anion-π interactions can improve the water solubility of AIE photosensitizers.Thus,here in this dissertation,a series of AIE photosensitizers with anion-π interactions were designed and synthesized.Their applications in photodynamic anticancer and antibacterial therapy were deeply studied.The main contents are as follows:1.By adjusting the conterion of AIE photosensitizer,a water-soluble type I photosensitizer（DPBC-Br）with anion-π interactions was synthesized and it can be applied in biological environments without any organic solvent and polymer coating process.DPBC-Br,with superior stability against photobleaching and high type I ROS generation capability,can be used for the NIR fluorescence imaging and discrimination of tumor cells from normal cells with a wash-free manner.In addition,targeted imaging from lysosome to mitochondria can be realized by regulating the concentration of DPBC-Br.Chemotherapy/PDT synergistic therapy can also be achieved for selective ablation of cancer cells.This work about rational construction water-soluble type I AIE photosensitizer would provide a pioneering reference for targeted NIR fluorescence imaging and PDT of hypoxic tumor cells in a wash-free manner.2.PDT has also been extensively researched in the antibacterial field in recent years.Based on the excellent water solubility,near infrared emission and efficient ROS production ability,DPBC-Br photosensitizer is used for the study on PDT against Staphylococcus aureus and multidrug-resistant Staphylococcus aureus.Experimental results showed that DPBC-Br can bind to proteins on bacteria surface to realize NIR fluorescence imaging and photodynamic antibacterial against Staphylococcus aureus and multidrug-resistant Staphylococcus aureus.Therefore,DPBC-Br is a very promising PDT photosensitizer to deal with the threat of multidrugresistant pathogen infections.3.In order to improve the safety of photosensitizer to patients,we designed an AIE photosensitizer（DPBC-5F）with anion-π interactions that can respond to p H.By introducing pentafluorophenyl,DPBC-5F can covalently bind with thiol-containing proteins,which shorten the action distance between photosensitizer and substrate,effectively improve the efficiency of reactive oxygen species and reduce photosensitizer leakage.DPBC-4FSG is obtained after DPBC-5F reacts with the overexpressed glutathione（GSH）in tumor cells.The results showed that there was no significant difference in ROS production ability between DPBC-5F and DPBC-4FSG at acidic environment,but the ROS production ability of DPBC-4FSG decreased significantly at normal physiological conditions.Therefore,DPBC-5F has strong ROS production ability in tumor tissues,and is nontoxic to normal tissues,which can efficiently avoid the photoinduced cytotoxic side effect.