| Tumors have become a serious hazard to human health,and a variety of methods have emerged for the treatment of tumors.In particular,the combined treatment of various methods based on the characteristics of the tumor microenvironment has become a new direction of current research.With the in-depth research and rapid development of nanomedicine,photodynamic therapy(PDT)has gradually become a very promising new therapies for cancer treatment because of its good targeting,small damage to normal tissues,low invasiveness,economy,and non-drug resistance.However,the effect of PDT treatment is limited by the accumulation of photosensitiz-ers(PS),poor tumor targeting and hypoxic tumor microenvironment.PDT requires sufficient oxygen supply and effective delivery of photosensitizers,but the hypoxic state of solid tumors will form a vicious circle with PDT.In addition,nanocarriers need to successfully achieve immune escape in vivo.How to design and synthesize appropriate nanocarriers to coordinately solve the hypoxia problem of solid tumors,completely avoid immune clearance in the body,and target photosensitizers to tumor tissues is a key issue that needs to be solved urgently in photodynamic therapy.Nano metal-organic framework materials(NMOFs)have become excellent nano-medicine carriers due to their convenient synthesis,adjustable structure,easy modification,regular pores,and large specific surface area.The coordination bond is easily degraded in the weakly acidic tumor microenvironment,which can realize the intelligent responsive release of loaded photosensitizers drugs etc,so it has a broad development and application space in the field of biomedicine.Based on the advantages of metal-organic framework(MOF)materials,this article focuses on the scientific problem of how to overcome the limitation of TME on photodynamic therapy,chemotherapy and other nano-drug treatment modes,and designs and prepares a biomimetic nano-delivery system to carry out collaborative treatment of tumors.The first chapter of this thesis summarizes the relevant treatment methods of tumors,and introduces in detail the principles and effect limiting factors of photodynamic therapy,the types of nano drug carriers,the current research status of nano metal organic frameworks(NMOFs)in the field of biomedicine,the characteristics of the tumor microenvironment and the research overview of the biomimetic nano-delivery system put forward the research background and research significance of the thesis.The second chapter of the paper is based on overcoming the problems of photosensitizer aggregation and hydrophobicity.We coordinate the photosensitizer meso-tetrakis(4-carboxyphenyl)porphine(TCPP)and 2-aminoterephthalic acid to Zr4+,and directly synthesize UiO-66-NH2@TCPP through a one-pot method.Then load doxorubicin hydrochloride(DOX)in its pores;verify the relevant properties to prove that the synthesized UiO-66-NH2@TCPP@DOX still maintains the advantages of metal-organic framework(MOFs)materials,it has a stable metal frame structure,which is easily degraded in a slightly acidic environment,and can release the drugs in it.At the same time,because the photosensitizer TCPP is used as an organic ligand to form NMOFs,it effectively avoids the aggregation of photosensitizers caused by conventional methods of loading photosensitizer,You can leave the NMOFs channel space to load the chemotherapy drug doxorubicin hydrochloride.Spectral analysis showed that the load of doxorubicin hydrochloride was 31%,and the load of TCPP was 10.9%.The third chapter of the thesis studied the in vitro anti-tumor activity of the synthesized UiO-66-NH2@TCPP@DOX using the mouse melanoma cell B16F10as a model.The results show that UiO-66-NH2@TCPP@DOX has a good ability to generate singlet oxygen both outside and inside the cell.The comparison of cytotoxicity experiments and living dead cell fluorescence staining experiments under light treatment and dark treatment conditions proves that it can obviously kill tumor cells in vitro,especially under 660nm laser irradiation,the cell survival rate is 55%,it shows that UiO-66-NH2@TCPP@DOX photodynamic combined chemotherapeutic drugs have better killing effect on tumor cells than single photodynamic therapy and chemotherapeutic drugs.The fourth chapter of the thesis is to overcome the limitation of the tumor microenvironment hypoxia on the photodynamic therapy and realize the immune escape of the drug-carrying system in the body.Constructed a bionic nano drug delivery system UiO-66-NH2@TCPP@DOX@CAT@M with self-supplying ability,connect catalase to the surface of UiO-66-NH2@TCPP@DOX through glutaraldehyde,and finally wrap a layer of tumor cell membrane on the surface of UiO-66-NH2@TCPP@DOX@CAT to synthesize oxygen-supply photodynamic therapy nano-drug delivery system with bionic function,UiO-66-NH2@TCPP@DOX@CAT@M,the coated cell membrane can not only escape the elimination of the host immune system,but also improve the homology targeting and enrichment ability of tumor tissues.Under laser irradiation,the photosensitizer TCPP exerts the effect of photodynamic therapy,and at the same time catalase catalyzes the hydrogen peroxide in tumor cells to produce oxygen,which solves the limitation of photodynamic therapy in the hypoxic microenvironment of solid tumors.Improve the effect of photodynamic therapy.,it is confirmed by in vitro cytotoxicity experiments,live dead cell fluorescence staining experiments and in vivo experiments in tumor-bearing mice,the nanoparticles we constructed have the effect of relieving tumor hypoxia.Through the combined effect of enhanced photodynamic therapy and chemotherapy,it effectively inhibits the growth of mouse melanoma.At the same time,the nanomedicine also shows good biocompatibility.The fifth chapter of the thesis summarizes the overall research content and proposes further scientific and technical issues that need to be resolved in this field. |
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