Application And Research Of Double Responsive Drug Delivery Systems Based On UiO-66-NH₂ And Sodium Polyacrylate Self-assemblies

In this paper,the pH and glucose stimuli-responsive drug delivery systems combined therapy,targeting and MRI imaging were researched,which were based on the metal organic framework nanomaterials(MOFs,UiO-66-NH2)and sodium polyacrylate(PAAs)self-assemblies as drug carriers.The paper mainly includes three chapters:In chapter one,a review of the preparation and application in nanobiomedicine of the metal organic framework(MOFs)nanomaterials and polyacrylic acid was described.Also,the research purpose and content of this paper are briefly described.In chapter two,two kinds of drug delivery systems based on the UiO-66-NH2 as drug carrier were constructed by borate ester bond linkage.(1)UiO-66-CBA-PVA nanocomposites were obtained by modification CBA molecules on the surface of UiO-66-NH2 nanoparticles,and then PVA films were capped on UiO-66-CBA by borate ester bond.The results from in vitro release assay showed that the leakage was only 20.99%after 48 h at pH=7.4,indicating that the PVA films had a good blocking effect.The release of DOX was 91.98%in reponse to the double stimulus of pH=5.0+10 mM glucose.MTT assay showed that the inhibition rate for HeLa cells rechived to 72.26%.(2)CeO2 nanoparticles were prepared by a-cyclodextrin molecules as stabilizer and RGD molecules as targeting molecules.Then,the drug delivery system based on UiO-66-CBA-a-CD-CeO2-RGD nanoparticles were prepared by crosslinking the UiO-66-CBA and a-CD-CeO2-RGD through borate ester bond.In vitro release test,the data showed that the leakage was only 9.1%after 48 h at pH=7.4,indicating that the capping efficiency of a-CD-CeO2 nanoparticles was better than of polymer film layer.In addition,DOX release could be up to 86.69%under the pH and glucose double stimulus.MTT assay showed that the inhibitory rate of HeLa cells was 90.31%in 48 h.Therefore,all the above results indicated that the UiO-66-NH2 nanoparticles could be as potential nano-drug carriers,because of its simple preparation process,low toxicity and high cell inhibition rate.In chapter three,different PAA chains were modified phenyl boronic acid(PBA)and glucosamine(Glu),respectively.Then,PAA-PBA-Glu-PAA(PPGP)nanospheres were prepared by using microemulsion self-assembly method and crosslinking the PBA and Glu through PBA-sugar interaction.By the coordination of carboxyl and Gd3+,the PPGP-Gd3+ system was established.The nanospheres exhibit a high drug loading(74.21%).Furthermore,the PPGP-Gd3+ nanospheres could be dissociated,triggered by acid and glucose stimulation in the microenvironment of tumor.The results from in vitro release test revealed that the drug release was 73.98%in reponse to pH=5.0+10 mM glucose.The r1 value of PPGP-Gd composite nanospheres was up to 34.34 mM-1·S-1.Therefore,with high drug loading,double stimulus response,MRI imaging and biodegradation,a multi-functional drug release system based on PPGP-Gd3+ nanospheres was established.