Synthesis Of Composites Based On Up-conversion Materials And Study On The Application As Multifunctional Drug Carriers

Rare earth doped up-conversion luminescent materials are a kind of luminescent materials that have attracted much attention.Compared with the traditional fluorescent materials,including organic fluorescent dyes and quantum dots,up-conversion materials can not only overcome the background interference,reduce the damage of light on organisms,increase the light penetration depth,also shows fine biocompatibility,good light stability.Because of unique structure and luminescent property,this kind of materials show a promising prospect in the field od bioimaging.Recently,up-conversion luminescent materials have been widely used in drug carrier,bioimaging,biosensor,photodynamic therapy,photothermal treatment etc.In this work,we synthesize a series of rare earth doped up-conversion materials and explore the conditions of synthesis to optimize the properties in the application of drug delivery and bioimagin,which is aimed to synthesize multifunctional drug carriers for simultaneously imaging and pH-responsive drug release.The main contents of are as following:In the first chapter,the research background of drug carrier,rare earth doped up-conversion luminescent materials and metal-organic frameworks are introduced,including the concept,structure characteristics,properties,synthesis methods,and the latest research progress.On basis of the research propgress,the ideas and purpos of the design are exhibited.In the second chapter,UCNPs particles are controllable synthsized and further coated with MOFs to form multifunctional drug carriers.Firstly,the controllable synthesis conditions of up-conversion nanoparticles NaYF4:Yb3+,Tm3+(UCNPs)are discussed.The UCNPs with small size,uniform morphology and good stability are obtained.The morphology and structure of the UCNPs are confirmed by XRD,FT-IR and SEM.Secondly,based on the optimal UCNPs,coated with MOFs and polymer PEG,the novel core-shell composites UCNPs@MIL-PEG is generated.Finally,the structure and properties of the composites are discussed.The UCL and MRI results indicate that UCNPs@MIL-PEG has outstanding dual-model imaging property.In this experiment,the anticancer drug doxorubicin hydrochloride(DOX)is used as drug model. Compared with UCNPs@MIL,the loading percentage of UCNPs@MIL-PEG is 60%,which is improved 27%.It shows that UCNPs@MIL-PEG has better drug loading capacity.UCNPs@MIL-PEG also shows better pH-resposeive drug delivery capacity.The drug release of UCNPs@MIL-100 reaches at 60%at pH 7.4 after 30 h and 80%after 50 h.In comparison,the drug release of UCNPs@MIL-PEG reaches less than 20%at pH 7.4,All the results prove good biocompatibility,excellent performance in dual-model imaging and pH-responsive drug release of UCNPs@MIL-PEG.In the third chapter,a novel rare earth doped metal-organic frameworks(called Up-MOFs)RE(BTC)(H2O)·DMF(Up-MOFs)is prepared,further modified by SiO2 and FA to improve the drug loading capacity and targeting drug release.Firstly,Up-MOFs that doped with Tm3+and Gd3+is firstly prepared using one-pot hydrothermal method.In this work,uniform Up-MOFs particles are obtained through the change of the condition,including the amount of surfactant and capping agent,the hydrothermal reaction time and temperature.The morphology and structure of Up-MOFs are characterized by XRD,FT-IR and SEM methods.Secondly,on the basis of the optimal Up-MOFs,mesoporous SiO2 shell and folic acid(FA)are coated on the surface to form Up-MOFs@SiO2-FA.The structure,up-conversion luminescence and MRI properties of the composites are discussed.Finally,the performance of UCL and MRI indicate that Up-MOFs@SiO2-FA has outstanding dual-model imaging property.DOX is used as drug model to explore the drug loading and release properties of Up-MOFs@SiO2-FA.The drug loading amounts of Up-MOFs@SiO2-FA composites is 41.5 mg/g.The DOX release from Up-MOFs and Up-MOFs@mSiO2-FA at pH 5.8 are both faster than that at pH 7.4,indicating pH-responsive drug release.The total drug release of Up-MOFs is 40%at pH 5.8 and 18%at pH 7.4.In comparison,the DOX release of Up-MOFs@mSiO2-FA is 64%at pH 5.8 and 12%at pH 7.4.Clearly,Up-MOFs@SiO2-FA shows better pH-responsive DOX release.All the results show that Up-MOFs@SiO2-FA not only has good biocompatibility,but also integrates dual?model imaging,pH-responsibility with targeted drug release.In the fourth chapter,the solvothermal method is applied to controllable synthesize of the up-conversion nanoparticles with hollow structure,further functional modified to build binary-drug delivery system.Firsly,polyethyleneimine(PEI)modified NaYF4:Yb3+,Tm3+(hollow UCNPs)is designed and prepared by one-step hydrothermal method.Through the regulating of hydrothermal reaction time and Gd3+ doping ratio,hollow UCNPs with small particle size,uniform morphology and good fluorescence properties are synthesized.The morphology and structure are characterized by XRD,FT-IR and SEM methods.Secondly,in order to reduce the drug resistance and improve the efficiency of drug delivery,a novel dual drug delivery system is designed:With hollow UCNPs as core,loaded with DOX,then modified with chitosan(CS)as shell,loaded with methotrexate(MTX),a dual drug delivery system UCNPs/DOX@CS/MTX is obtained.The porous structure and properties of the nanocomposites are confirmed by a series of tests.The experimental results show that hollow UCNPs/DOX@CS/MTX not only has excellent loading capacity,also exhibits a remarkable performance of pH-responsive drug release.Imaging in cells and mice show excellent UCL/MRI imaging properties.Therefore,hollow UCNPs/DOX@CS/MTX integrates dual model imaging,dual drug loading and pH-controllable drug release,which is hopefully to provide theoretical basis for multifunctional drug carrier for diagnose and treatment.