Synthesis And In Vitro Biological Activities Of Phthaloyanines-Based On Photodynamic Therapy

Phthalocyanine(Pc)as a synthetic derivative of natural porphyrins,is one of the most promising photosensitizer(PS)for photodynamic therapy.It has the characteristics of red light absorption,strong tissue penetration,good stablility,high yield of singlet oxygen and rapid metabolism in vivo.However,Pcs have a planar conjugate structure so that Pcs poor solubility in aqeous solution,hard to purifiy.It is possible to greatly improve the aggregation state of the Pcs by connecting a water-soluble group such as a carboxyl group.In recent years,more and more studies have confirmed that germanium,molybdenum,palladium,copper,other metals and their complexes also have anti-tumor,anti-bacterial activity.However,poor solubility of these chemotherapy drugs,long-term use of drug resistance,toxicity need to be solved.In this thesis,we synthesize water-soluble CuPc and NiPc.The biocompatible Pcs were used as carrier to modify the solubility.Their physical,chemical properties and in vitro properties are investigated to achieve the effect of chemotherapy and photodynamic therapy in anticancer and anti-cancer.The second part of this thesis,axially substituted SiPc with quaternary amine ring has been sythesized.The functionalization of axial position enhances steric hindrance to improve solubility.Through access SiPcs to improve biocompatibility,get high yield of singlet oxygen and get an efficient photosensitizer for photodynamic therapy.The results are as follows:1.Synthesis of water-soluble CuPc,NiPc.It is found that the addition of the raw materials and the catalyst to the reaction then add metal salt,this method can efectively improve the purity and yield of Pcs,especially for CuPc.The synthesized Pcs are characterized by1H NMR,MS,IR and UV-Vis spectroscopy.The successful synthesis of water-soluble Pcs are demonstrated.2.The photophysical chemical properties of these Pcs,the yield of singlet oxygen,photostability assay and water solubility are studied.The cellular uptake of CuPc towards Hela cells is about one third of Nipc.In the cytotoxicity test,two water-soluble Pcs show cytotoxicity in both light and dark,indicating that heavy metals could inhibit tumor cells.At the same time,the IC50 value under light conditions is significantly lower than that of the dark condition,which shows Photodynamic-Chemotherapy Synergistic Anticancer Activity.3.SiPc-(Cyclen)2 is designed and synthesized by using Cyclen as the raw material,which have been characterized through NMR(1H,13C),UV-Vis spectra.The photophysical and photochemical properties of the singlet oxygen yield and fluorescence quantum yield of the compounds are subsequently tested.The results shows that the synthesized SiPc had solubility in the organic solvent,and the low concentration is in accordance with Beier-Lambert's law.The yield of singlet oxygen is 0.47 and the fluorescence quantum yield is 0.37,which indicates that the synthesized SiPc has some advantages as PS.4.In vitro cytotoxicity and fluorescence imaging of SiPc-(Cyclen)2 is studied in Hela cells.The cellular uptake of SiPc-(Cyclen)2 shows that it can get in the Hela cells.Intracellular fluorescence imaging experiments shows that our SiPc can be well distributed in Hela cells.In the cytotoxicity test,the synthesized SiPc shows good phototoxicity and very low dark toxicity,with an IC50 of 0.20 ?M.Therefore,this SiPc could be potentially as PS for PDT,with potential application value.