Synthesis Of High Water-soluble Conjugated Polymer Brush For Photodynamic Cancer Therapy

Photodynamic therapy has become a new method for tumor therapy because of its low toxicity,small damage to normal tissue and obvious effect in cancer prevention.However,the absorbability of traditional photosensitizer is poor and it is also not easy to modify,which limits the effect of photodynamic therapy.Conjugated polymers have the characteristics of good optical stability,strong light absorption and easy to chemical modification which used to prepare photosensitizers.It is reported that the conjugated polymer photosensitizer still has the defect of poor water solubility and lack of active targeting to the tumor.In this paper,the water-soluble polymer is introduced into the pendant groups of the conjugated polymer to improve the water solubility of the polymer.The functional sugar polymer is introducted to the side chain of the water-soluble polymer to improve the ability of active targeting.The specific contents of this paper are as follows:(1)Preparation of high water soluble brush conjugated polymer photosensitizer(PPF-Ir-g-POEGMA): Firstly,the iridium complex(ppy)2Ir(BrFPyBr)was introduced into the polyfluorene conjugated backbone by Suzuki polymerization,and then the ATRP polymerization was used to connect the water-soluble polymer(PO EGMA)to achieve the water solubility of the polymer.The doping ratio of the main chain iridium complex is 33% and the number of OEGMA introduced to the side chain is 10.Emission spectrum of the polymer showed that there were two emission bands in the 390-510 nm and 570-700 nm.The solubility of the polymer in aqueous solution was 10 mg/mL and the mean grain size was 168 nm measured by DLS in the aqueous solution.This demonstrated that the conjugated polymer has good dispersibility in water.Finally,the active oxygen probe(ADMA)was used to detect the single-phase oxygen,after light for 210 seconds ADMA almost consumed completely,proving that the photosensitizer can efficiently produce single-phase oxygen,with the potential of photodynamic therapy.(2)Glycopolymers-containing brush-type polymer as a photosensitizer for Hep G2 tumor targeted photodynamic therapy: In order to achieve the active targeting for HepG2 cells of the photosensitizer,we introduced the second block galactose polymer to the POEGMA by click chemistry to obtain the PPF-Ir-g-(POEGMA-b-PGal),and then we studied the targeting of photodynamic therapy for HepG2 cells.First,the singlet oxygen was measured by ADMA,which indicated that the photosensitizer produced a high rate of singlet oxygen after irradiated.MTT assay showed that HepG2 cells and Hela cells had low cytotoxicity at polymer concentration of 0.5 mg/mL.The targeting of PPF-Ir-g-(POEGMA-b-PGal)to Hep G2 cells was induced by the interaction between galactose polymer and ASGP-R proved by flow cytometry and laser confocal microscopy.Further,the experiments showed that PPF-Ir-g-(POEGMA-b-PGal)can produce singlet oxygen in HepG2 cells.Photodynamic therapy was performed by flow cytometry and laser confocal imaging.After irradiation,the percentage of apoptosis was more than 80%,showing a good photodynamic therapy effect.The targeting property was demonstrated again by comparing the photodynamic MTT assay of Hep G2 and Hela cells with PPF-Ir-g-(POEGMA-b-PGal).Finally,polymer was injected to Hep G2 tumor-bearing mice for photodynamic therapy.The volume of mice tumor was significantly reduced and the effect of photodynamic therapy was obvious.(3)Ir/PGlc-NP and Ir/?-1,3glucan-NP were prepared by coated method using iridium complex as the core structure,glycopolymers and polysaccharide as shell structure respectively.Its particle size,spectrum and morpho logy and other properties were characterized respectively.Nanoparticles were injected into the mice through tail vein.After 24 h,the fluorescence imaging of the mice was performed.The results showed that the fluorescence signals were mainly concentrated in the liver,and the lungs and kidneys also had little fluorescence.These results demonstrated that the nanoparticles can be used as a fluorescent probe for a series of biomedical applications in vivo.