Design,Synthesis And Application Study Of Phosphorescent Nanoprobes Based On Porphyrin And Phthalocyanine Derivatives

Cancer is now a serious threat to human health in the worldwide,which together with cardiovascular disease have become the two major problems facing by medicine.Hence,the diagnosis and therapy of cancer is growing to be a research hot spot in the field of materials,chemistry and biomedicine,etc.Diagnostic technologies usually include various invasive tumor imaging techniques,such as magnetic resonance imaging,ultrasonic imaging and fluorescence imaging,etc.The morphology and metabolism information of tumor tissue can be diagnosed by these technologies.Among these imaging technologies,fluorescence imaging technique is of many merits such as high sensitivity,less side effects,no radioactive reagent,operation simply,which therefore have the higher safety.As far as the cancer therapy technologies are concerned,photodynamic therapy(PDT)is one of the newly emerging tumor treatments and developing rapidly,which holds advantages of good tumor targeting,less side effects and no harm to the normal organs of patients.It requires three basic elements in PDT: photosensitizer(PSs),excitation light and molecular oxygen.Porphyrin derivatives are a kind of traditional photosensitizers and have been approved to apply in clinical cancer treatment in many countries.PtII and PdII porphyrins,in particularly,received great attention due to their high phosphorescence quantum yields,long triplet state lifetime,large stokes shift and favourable photostability,which therefore are of great research values as phosphorescent probes.Phthalocyanine derivatives are another class of photosensitizers and have attracted numerous attention because of their simplicity of synthesis,chemical stability,strong absorption in range of 600-700 nm which is 20-50 times of porphyrins,non-toxicity,selectively retention and strong lethality to the tumor tissue but less effect on the surrounding normal tissue.However,conventional PSs have obvious drawbacks.Such as most phthalocyanine and porphyrin derivatives have poor solubility in water,and most PSs could also accumulate in normal tissues due to the lack of specificity.In addition,they could easily aggregate in aqueous media,resulting in aggregation-caused fluorescence quenching,which limits their application in biomedicine.Therefore,in this thesis,we dedicated to synthesize several series of theranostic biological nanoprobes based on metal porphyrins and metal phthalocyanines with high water-solubility.The main contents of this thesis include: 1.Design and synthesis of porphyrin-based small molecules(PtTPP and PdTPP)and metallopolymers(Pt-P and Pd-P).PtTPP NPs,PdTPP NPs,Pt-P NPs and Pd-P NPs were prepared by using reprecipitation method.The structure and properties of these NPs were well characterized by nuclear magnetic resonance(NMR),infrared spectroscopy(FT-IR),dynamic light scattering(DLS),UV-vis spectroscopy,photoluminescence spectroscopy(PL)methods.The confocal laser scanning microscopy(CLSM)images demonstrated that Pt-P NPs are suitable for labeling HeLa cells.With the decrease of the oxygen concentration,the fluorescence lifetime of HeLa cells labled with Pt-P NPs was elongated.However,these nanoparticles aggregate together extracellularly,which influence the cellular imaging quality.Therefore,it is necessary to further improve the water-solubility of porphyrin-based metallopolymers and enhance its biocompatibility.2.Design and synthesis of high water-soluble PtTCPP@b-CD and PdTCPP@b-CD through surface modification of metal porphyrins with b-CD.The surface electricity of PtTCPP@b-CD and Pd TCPP@b-CD was further modified by using CTAB,which turns out that the surface potential of PtTCPP@b-CD@CTAB and PdTCPP@b-CD@CTAB was changed from negative charging to positive charging through the examination results of Zeta potential.The structure and properties of Pt TCPP@b-CD@CTAB and PdTCPP@b-CD@CTAB NPs were also well characterized by 1H NMR,FT-IR,DLS,UV-vis,PL.MTT experiments show that these two NPs have low biological cytotoxicity.CLSM images indicate that PtTCPP@b-CD@CTAB and PdTCPP@b-CD@CTAB NPs can target recognize cancer cells and show strong red fluorescent emission with higher concentration,which endows them great application perspective in cancer diagnosis.3.Design and synthesis of Pt TCPc@b-CD and Pd TCPc@b-CD through surface modification of metal phthalocyanines by using b-CD,which improved the water-solubility of metal phthalocyanine derivatives successfully.Surface potential of PtTCPc@b-CD and PdTCPc@b-CD was also modified through using CTAB to change negative charging to positive charging.The structure and properties of PtTCPc@b-CD@CTAB and PdTCPc@b-CD@CTAB NPs were well characterized by 1H NMR,FT-IR,DLS,UV-vis,PL.MTT experiments show that PtTCPc@b-CD@CTAB and PdTCPc@b-CD@CTAB NPs are also less biological cytotoxicity.CLSM images demonstrate that PdTCPc@b-CD@CTAB NPs are of good near infrared imaging property.