Preparation Of Composites Based On MOFs And Study On The Application As Drug Carriers

Metal organic frameworks?MOFs?are a kind of organic-inorganic composite materials constructed by metal ions and organic ligands.So the materials integrate the features of inorganic and organic compounds at the same time.These new composites develop rapidly in the field of coordination chemistry in last decade.MOFs are famous for its porous,which has been widely used in many fields,such as nonlinear optics,gas adsorption,catalysis and chemical sensors etc.It is demonstrated that MOFs have been a promising carrier for anticancer drug,because that they possess numerous advantages like large drug dosage,high porosity and tunable functionality.Nevertheless,there is the limitation of the single MOFs as drug carrier,for example low biocompatibility,not targeted release,unsatisfactory controlled release etc.In this paper,a variety of functional metal organic framework materials were designed and synthesized.Integrated MOFs with other materials remedies the limitation of single MOFs in order to achieve multifunctional.The structure of the materials is characterized by XRD,IR,SEM and TEM,and ibuprofen?IBU?and doxorubicin hydrochloride?DOX?is regarded as drug models to realize the controlled drug release at different pH values.The paper is mainly divided into four chapters.In Chapter 1,it firstly summarized the research background of metal organic frameworks that included the definition,structure and synthesis method of MOFs materials,and the latest researches development in luminescence,ion exchange,catalysis and gas selective adsorption etc.And then,the deficiency of the single MOFs application in the biomedical field was discussed,and introduced some creative work made up for these disadvantages of MOFs.Finally,this paper briefly introduced the design and synthesis of composite materials based on MOF in the three topics of this thesis.In Chapter 2,Cu-MOFs with mixed ligands were synthesized by hydrothermal method,and different MOFs could be obtained by adjusting the ratio of mixed ligands.The morphology and structure were confirmed by XRD,FT-IR and SEM,TEM characterizations.It was found that the structures of different Cu-MOFs were totally different and could be controlled through the change of the ratio.IBU and DOX were selected as drug models to study the drug loading and drug release of different MOFs.It showed that MOFs-2 was with the largest drug loading among the materials.The drug loading for IBU was 70 mg/g and that for DOX was 95 mg/g.In order to study the drug releasing properties of MOFs-2 with mixed on these two drugs,the release experiment of ibuprofen and doxorubicin loaded MOFs-2 were simulated in vitro respectively.IBU release experiment in PBS indicated that IBU could release more continuously and stably.DOX released more rapidly and almost completely in pH 3.8 buffer solution.While DOX released little in pH 7.4,indicating a good pH controlled release effect.All results showed that the MOFs-2 was an ideal drug carrier material with excellent drug loading,and can satisfy the needs of different drug release.In Chapter 3,magnetic composite materials based on MOFs were prepared.?-Fe₂O₃ particles were obtained by coprecipitation method,?-Fe₂O₃/MOFs materials were prepared via solvothermal method and further coated by Si O₂ to form novel core-shell composite materials?-Fe₂O₃/MOFs@SiO₂.The structures of the composites were confirmed by XRD,FTIR and TEM characterizations.The materials were proved to be magnetic by external magnetic field.The excellent fluorescence properties of the La-MOFs were examined by fluorescence detection.The drug loading and in vitro drug release properties of?-Fe₂O₃/MOFs@Si O₂ were investigated by selection of IBU and DOX as drug models.Experiments results demonstrated that the composites were with excellent drug loading for IBU?70 mg/g?and DOX?80 mg/g?.For the release of IBU,the release rate in the pH=7.4 buffer was stable and lasting for 6 days until the complete release,indicating a good sustained release effect.For the release of DOX in pH 7.4 buffer solution,DOX can be only partly released?30%?,while in pH 3.8 buffer solution,DOX can be fully released,and the release rate reached 50%within 12 hours.The nanoparticles can be loaded with different drug models simultaneously,and can meet the different needs of different drug release.It can also be administered by magnetic targeting,and the fluorescence intensity is also expected to monitor drug delivery.In Chapter 4,a novel drug delivery system?MOFs/CDs@OCMC?with integration of diagnosis and treatment was designed and synthesized.As the center of this system,MIL-100?Fe?was with excellent drug loading and the large amount of Fe³⁺in its structure made it as magnetic resonance imaging contrast agent.Carbon dots?CDs?encapsulated into the synthesized MOFs endowed fluorescence features to the nanoparticles,which could be used for fluorescence imaging.The coated carboxymethyl chitosan?OCMC?can greatly enhance the biocompatibility of the composites and endow them with pH response.The structural characteristics were studied by means of XRD,IR,SEM and TEM characterizations.Magnetic resonance imaging?MRI?and fluorescence imaging?FOI?of MOFs/CDs@OCMC were investigated and proved to be used for MRI and FOI contrast agents.The results showed that the material could be used for MRI/FOI dual mode imaging,which can improve the sensitivity of diagnosis.Doxorubicin hydrochloride?DOX?was selected as drug model,anticancer drug loading and release on the composite material were discussed.The experimental results showed that the nanoparticles were with higher landing for DOX.Moreover,DOX can release fast and completely in pH 3.8 buffer solution,while release little in pH 7.4.Thus pH responsive can be achieved.The nano composite particles not only had large drug loading and low toxicity,but also could be MRI/FOI contrast agents.The new drug delivery system with integration of diagnosis and treatment was obtained and it is a promising drug carrier,which could not only meet the high drug loading and low toxicity of drug carrier,but also could be used for MRI/FOI dual-mode imaging and pH control release.