Synthesis And Biological Activities Of Phthalocyanine-Based Nanomaterials For Synergistic Photodynamic/Photothermal Therapy

Given the limitations of traditional treatments,there is increasing interest about new approaches to cancer treatment.Photodynamic therapy(PDT),as one of the new therapeutic methods,has the advantages of noninvasive,improved tumor targeting nature,enables to be treated repetitively and reduced side effects.However,a tipe of the defining characteristics of tumors is hypoxia,which would tremendously suppress the efficiency of PDT,especially when oxygen is gradually exhausted as the treatment progresses.Hence,integrating PDT with other therapies to improve treatment efficacy is receiving much more attention.Photothermal therapy(PTT)involves cell damage by heat generated from PTT agent via conversion of light absorption.When the two methods are simultaneously performed in cancer cells,the blood circulation is accelerated as the temperature of the tumor increases,and the oxygen content in the cancer cells can be increased,thereby improving the therapeutic effect of PDT.Therefore,combining the two treatment methods can achieve a therapeutic effect of 1+1>2.The most straightforward and effective way to combine the two treatment modalities is to combine the photosensitizer with the photothermal material.Silicon phthalocyanine(SiPc)has wonderful photoactivity and biocompatibility and has been used in many studies.Since the silicon in the center of the silicon phthalocyanine allows it to be modified by introducing ligands in the axial direction,thereby achieving different functions,such as increase the solubility of the silicon phthalocyanine in water and increase the stability in vivo.Compared with precious metal photothermal material,graphene oxide(GO)are low cost,and convenient preparation from graphite,water-solubility and plentiful surface functional groups(carboxylic,epoxide and hydroxyl groups),enabling it easy to be modified.Therefore,it is an ideal photothermal material for the preparation of dual-modality agents.According to the above background,in this thesis,an amino axially substituted silicon phthalocyanine was synthesized,and silicon phthalocyanine nanospheres(NanoSiPc)and silicon phthalocyanine-graphene oxide nanomaterials(SiPc-GO)were prepared by self-assemblyand covalent bond respectively.Those nanomaterials capable of fluorescence imaging and combined photodynamic and photothermal therapy.The detailed information of this thesis are as follows:1 Amino silicon phthalocyanine was synthesized,the structure of the sample was characterized through NMR,UV-vis and F.I.spectroscopy.The obtained SiPc-NH2 was dissolved in DMF and through self-assemblyand to obtain an aqueous solution of NanoSiPc.Electron micrographs of NanoSiPc were obtained by AFM,SEM and TEM.The photodynamic and photothermal therapy effects of NanoSiPc were evaluated by testing the singlet oxygen generate and photothermal effect of NanoSiPc in deionized water.In vitro cytotoxicity and fluorescence imaging are carried.The results show that NanoSiPc can perform photodynamic and photothermal therapy in cells,leading to apoptosis of cancer cells.Meanwhile,it can produce red fluorescence in cells and fluorescently label cancer cells.In vivo,NanoSiPc was introducing into the mice by tail vein injection.The biocompatibility and in vivo therapeutic effects of NanoSiPc were tested in experiments.The results show that NanoSiPc can effectively inhibit and eliminate tumors in mice.2 The amino silicon phthalocyanine and the graphene oxide conjugated by covalent bond through amide reaction to form SiPc-GO.The UV-vis,FT-IR,Raman spectra were used to examine the chemical structure of the SiPc-GO.The morphology and size of SiPc-GO were observed by AFM and DLS.The singlet oxygen generates and photothermal effect of SiPc-GO in the solution were tested,and its therapeutic effect and fluorescent labeling effect in cancer cells were also studied.In vitro,it was found that SiPc-GO can efficiently perform photodynamic/photothermal therapy and intracellular fluorescence imaging in cells,The SiPc-GO was introduced into the mouse by tail vein injection,and the therapeutic effect in vivo was observed.The results show that SiPc-GO can induce the inhibition of tumor growth violently.