Research On Antibacterial And Drug Release Based On Water-soluble Conjugated Polymers

Water-soluble conjugated polymers(WSCPs)were widely used in biological sensing,cellular imaging,drug release and cancer diagnosis due to its advantages of good water solubility,high fluorescence quantum yield and easy modification.Under the light irradiation,WSCPs,as good photosensitizers,can sensitize the surrounding oxygen to produce reactive oxygen species(ROS)for antibacteria and tumor treatment.In this thesis,four kinds of WSCPs were designed and synthesized.The production rate of ROS,antibacterial activity of WSCPs and structrue-activity relationship were investigated to design conjugated polymers with better antibacterial activity in the future.In addition,a new WSCPs probe was synthesized using disulfide' bond to link anticancer drug on the end of conjugated polymer's side chain.This probe not only can detect drug release in real-time,but also can be used for antitumor by combining the chemotherapy and photodynamic therapy.The results are as follows:1.Study on antibacterial activities and structure-activity relationship based on cationic conjugated polymersConjugated polymers are widely used in antibacteria based on photodynamic therapy,but their structure-activities relationship has not been reported.Herein,four kinds WSCPs,poly(fluorene-co-phenylene)(PFP)and poly(fluorene-co-phenylene ethynylene)(PFE-1,PFE-CN-2,PFE-NP-3)were designed and synthesized.The ROS production rate,antimicrobial activities and structure-activities relationship were studied.The research results indicated that antibacterial activities of all WSCPs against the bacteria model of E.coli are dependent on the light irradiation intensity and irradiatin time.Furthermore,it is found the order of antibacterial effects of four WSCPs against E.coli is as follows:PFE-CN-2>PFE-1>PFE-NP-3 ? PFP.The difference of antibacterial activities mainly results from the production rate of ROS of WSCPs.The faster ROS are produced,the better antibacterial activities of WSCPs are.Among these four WSCPs,PFE-CN-2 produce ROS with the fastest rate,leading to the best antibacterial performance.Due to electron-withdrawing group,2,4-dinitrobenzenesulfonyl,being linked as a side chain of PFE-NP-3,PFE-NP-3 fluorescence is quenched by PET effect.Also,this group could make PFE-NP-3 produce ROS slowly,resulting in the poorer antibacterial activities of PFE-NP-3.In conclusion,we found poly(fluorene-co-phenyleneethynylene)can produce ROS faster than poly(fluorene-co-phenylene),and that introducing electron-withdrawing groups to the side chain of conjugated polymers can reduce the production rate of ROS.In addition,the antibacterial activities of WSCPs enhance with increasing the light irradiation intensity and time.This work is helpful for designing conjugated polymers with better antibacterial activities in the future,and provides new methods for pathogen therapy using conjugated polymers-based photodynamic therapy.2.Study on real-time drug deliver monitoring and anti-tumor therapy based on conjugated polymersFirstly,the conjugated polymer PFE-S-S-COOH with disulfide bond and carboxyl group on the side chain was designed and synthesized.Then the water-soluble conjugated polymer PFE-S-S-DOX were obtained by linking anticancer drug doxorubicin(Dox)to the side chain of conjugated polymer by virtue of carboxyl-amino reaction.Taking advantage of the photoelectric properties of conjugated polymers and glutathione reduing disulfide bond,this new probe could realize real-time detection of drug release and can combine chemotherapy and photodynamic therapy for tumor treatment.The Dox contains one quinone group that is a highly efficient electron transfer(ET)quencher,resulting in the fluorescence of conjugated polymer being quenched through the ET effect.In the presence of glutathione,the disulfide bond can be cut off by glutathione,which induces the fluorescence of PFE-S-S-DOX recovering and Dox being released for chemotherapy.At the same time,under the light irradiation,the conjugated polymer also can produce ROS for tumor treatment based on photodynamic therapy(PDT).Accordingly,the PFE-S-S-DOX not only can be used for real-time monitoring of drug release,but also could combine chemotherapy with PDT to improve the effect of antitumor.The research results indicated that the fluorescence of PFE-S-S-DOX recovers after adding glutathione,and it reaches the plateau when the reaction time is 60 min.The selectivity and the antitumor effect of the PFE-S-S-DOX polymer are still being investigated.