Application Of Metal Organic Frameworks In The Controlled Drug Release System

Metal-Organic Frameworks(MOFs)were new types of porous metal organic hybrid materials.Compared with traditional inorganic mesoporous materials,MOFs has great potential application and research value in the field of drug carrier.The main research of this paper was focused in the preparation,characterization and application of MOFs nanomaterials as drug carriers to control drug release.The paper mainly includes four chapters:In the first chapter,the development and application of MOFs in various fields was introduced in detail.Meanwhile,the selected topic and content of this thesis were briefly described.In the second chapter,a release system combining photo-thermal therapy,chemotherapy and targeting were prepared by using ZIF-8@PDA-FA nanocomposites as carrier.The above nanocomposites were gained by modification of PDA and FA molecules on the surface of ZIF-8 nanoparticles.After that,using DOX and ICG as model drugs,ZIF-8-ICG@PDA-DOX-FA nanocomposites were gained.Experimental results show that the PDA shell not only enhanc bioaffinity of nanocomposites,increase drug loadings,but also benefit the modification of target molecules on the nanocomposites.With addition of 100 ?g/ml of ZIF-8@ICG nanocomposites,the temperature of the simulated body fluid could increase by 16 ? under 2W/cm2 808nm laser,which mean that the ZIF-8@ICG nanocomposites have relatively high photothermal conversion rate.Data from MTT assay showed that the cell inhibition was 66%in the presence of ZIF-8-ICG@PDA-DOX-FA nanocomposites.As a result,combination treatment with ZIF-8-ICG@PDA-DOX-FA nanocomposites could provide effective treatment with minimal side effects.In the third chapter:UIO-66-NH2@sgc8 nanoparticles were employed as drug carrier to establish a drug delivery system which exhibit pH and specific response.The aptamer(sgc8)which would be "cap" and targeting molecule,was adorbed on the UIO-66-NH2 nanoparticles surface by electrostatic interactions.The results from in vitro release assay showed that the drug release was only 7.1%in pH=7.4 buffer with random DNA(rDNA).However,the release could be 32.1%once the rDNA was replaced as complementary DNA(cDNA).When the nanocomposites was in pH=5.0 buffer with cDNA,the drug release was reached to 64.9%,which demonstrated that the UIO-66-NH2@sgc8 nanocomposites could be triggered by pH and specificity stimulation.In the fourth chapter:ZrCl4 as metal salt,4,4'-dithiodibenzoic acid as organic ligand,UIO-67-S-S nanoparticles were prepared by coordination and precipitation.The obtained UIO-67-S-S nanoparticles are nanorods and the value of their specific surface was 441.67 m2/g.In order to cap and enhance the targeting of the UIO-67-S-S nanoparticles,PDA and FA molecules were modified on the surface of the nanoparticles in sequence.So far,most of the known MOFs were only pH-controlled degradative.However,the results from our in vitro release assay showed that the prepared UIO-67-S-S nanoparticles were in reponse to acid and reducing solution in the same time.Furthermore,MTT assay showed the UIO-67-S-S nanoparticles were low toxicity.The above results demonstrated that the obtained UIO-67-S-S nanoparticles would have promising application in nanomedicine.