Preparation,Performance Control And Application Of New Rare Earth Fluoride@MOF Nano Scintillator

Malignant tumors threaten human health.The widespread presence of strong adverse reactions and poor prognosis of the traditional surgery,chemotherapy,radiotherapy,and other treatment methods have limited their application.With the advancement of tumor treatment methods,tumor immunotherapy is emerged as the new revolutionary tumor treatment method for precise treatment.In addition,photodynamic therapy(PDT)is also one of the most important adjuvant treatments for tumor treatment.It has the advantages of temporal and spatial controllability,minimal invasiveness,and high specificity.It can also effectively induce tumor immunogenic cell death(ICD),further leading to activate the anti-tumor immune response.However,the low tissue penetration depth of the traditional light-activated PDT and the immunosuppressive microenvironment of deep solid tumors have severely hindered the effect of tumor treatment.Therefore,it is highly desirable to construct a composite nanoprobe with deep tissue photodynamic/immune combined therapy function.In this thesis,we will combine the porphyrin Zr-based metal organic framework(Zr-MOF)with intrinsic photosensitizer characteristics and rare earth fluoride nano-scintillators to construct a new type of soft X-ray activated nanoprobe to solve the bottleneck problem faced by traditional light-activated PDT.The main results are listed as follows:(1)NaYF₄:Gd/Tb@NaYF₄core-shell structured scintillator nanoparticls(SNPs)were successfully prepared by high-temperature co-precipitation method,and a new in-situ polyacrylic acid(PAA)growth strategy was developed to grow Zr-MOF on rare earth cores to form the SNPs@Zr-MOF hybrid nanomaterial.Then further load the photosensitizer Rose Bengal(RB)to construct the soft X-ray activated SNPs@Zr-MOF@RB nanoprobe.The soft X-ray activated luminescence properties of the nanoprobe were systematically studied,and the radioluminescence intensity was improved by?1.4 times,through the core-shell structure.Based on fluorescence resonance energy transfer,the production of reactie oxygen species(ROS)in deep tissues(3 cm)activated by soft X-ray is realized,which breaks through the problem of low tissue penetration depth of the traditional light-stimulated PDT,and lays the foundation for further treatment of deep tissue tumors in vivo.(2)The bioapplication of SNPs@Zr-MOF@RB nanoprobes activated by soft X-ray was further systematically evaluated.The PDT stimulated ICD,release of eoplastic antigen and secretion of immune-activated damage-associated molecular patterns(DAMPs)were further investigated.The results reveal that the synergistic photodynamic and anti-tumor immunity therapy of deep tissue tumor is realized.And the immunosuppressive tumor microenvironment(TME)is also modulated,which provides a new strategy of developing soft X-ray stimulated nanoprobe for deep tissue anti-tumor immunotherapy.(3)SNPs@Zr-MOF@ICG nanocomposites were constructed via further combination of indole cream(ICG)with photothermal effect.The photodynamic and photothermal characteristics of the nanocomposites were studied.The results show that the SNPs@Zr-MOF@ICG nanocomposites have good photodynamic characteristics and ideal photothermal conversion efficiency(?31.5%),and successfully achieves in vitro photodynamic and photothermal combination therapy of tumor cells,providing new joint therapy strategy for further tumor treatment.