Construction Of NMOFs-based Composites And Its Applications In Biological Imaging And Tumor Therapy

As the second leading cause of death in the world,cancer is a serious threat to human life and health.Research on cancer treatment has become a global public health problem to be solved urgently.Nanoscale metal-organic frameworks(NMOFs)show great application potential in biological imaging and cancer therapy due to their unique properties of adjustable chemical composition,adjustable pore size,easy surface modification and biodegradability.However,current studies mainly focus on the drug loading/release behavior of NMOFs in chemotherapy,and there is still a lack of research on multi-functionalization,targeting and synergistic therapy of NMOFs,which are closely related to practical applications.Based on the above background,this thesis aims to construct NMOFs-based composites through designing and optimizing the integration mechanisms,and utilize the synergistic effect among components to effectively improve the performance in bioimaging and cancer therapy.The main research contents are as follows:Chapter 1:A series of hollow NMOFs(MBMs)with cavity sizes ranging from100 to 200 nm were successfully in situ obtained utilizing the instability of coordination bond in Fe-MOF and the competitive coordination ability of polyoxometalates and sulfides.Furthermore,the as-synthesized hollow NMOFs were used as drug delivery platform and magnetic resonance imaging(MRI)contrast agents.In vitro and in vivo experiments show that the hollow nanoparticles MBM-12h possess good magnetic resonance imaging ability,ultrahigh drug loading/release capacity,and the composite 5-FU@MBM-12h also display excellent tumor inhibition ability.More importantly,a new strategy of macro-porous NMOFs preparation by competitive coordination method is proposed.Chapter 2:Several chemotherapy-based synergistic therapy systems were constructed using in situ growth strategy,thereafter,their bioimaging and cancer therapy behaviors were investigated.(1)To introduce photodynamic therapy module,Ti O₂ nanoparticles with photocatalytic properties were grown in situ on the surface of UIO-67 nanoparticles.Subsequently,the anti-cancer drug DOX was encapsuled into the pores of UIO-67 to endow the ability of chemotherapy and fluorescence imaging,then the NMOF-based photocatalytic composite DOX@UIO-67@Ti O₂ was obtained.The photodynamic therapy mechanism of the system was revealed by capturing ROSs through dye degradation experiments.(2)The NMOF-based core-shell structural composite,Ca O₂@Fe/ZIF-90@TA,with self-supplying oxygen and MR imaging ability was constructed by in situ growth method combined with competitive coordination strategy.Chloroquine phosphate(CQ)and L-arginine(NO precursor)were encapsulated in the large cavity to introduce the modules of chemotherapy and enhanced chemo-dynamic therapy.At last,the NMOF-based composite Ca O₂@Fe/ZIF-90@TA-A/C with abilities of MR imaging and chemo/chemo-dynamic synergistic therapy was successfully synthesized.(3)The in-situ growth method combined with post-modification strategy were used to construct the core-shell structure of Cu-doped ZIF-8 coated Ca O₂ nanoparticles,then loading DOX and coating with HA to obtain Ca O₂/DOX@Cu/ZIF-8@HA as a therapy system for targeting chemo/chemo-dynamic synergistic therapy and targeting fluorescence imaging.The self-supplying oxygen ability of Ca O₂/DOX@Cu/ZIF-8@HA was confirmed by in vitro dissolved oxygen test,and its fluorescence imaging ability and tumor inhibition ability were evaluated by establishing cell imaging model and tumor-bearing nude mouse model.Chapter 3:Through the surfactant controlling method combined with the post-modification strategy,the NMOF-based composite CQ/Nd-MOF@HA,of which Nd-MOF nanoparticle loading CQ and surface coating HA was constructed.CQ/Nd-MOF@HA can realize the specific targeting chemotherapy and NIR-?bioimaging.As far as we know,it is the first time that nano Ln-MOF with lanthanide metal ions as luminescence center has been applied in NIR-?imaging in vivo.