Preparation Of Metal-organic Frameworks Materials And Its Application In Photodynamic Therapy

Metal-organic frameworks(MOFs),a novel porous materials,have a great deal of application potentials and practical research values in the field of nano-drug carriers.ZIF-8 is a highly permeable porous material whose organic framework components are imidazole compounds which are acid-labile;UiO-66 is a common MOFs material that can be applied to post-synthetic modification.Photodynamic therapy(PDT)is a novel method for treating tumors.The principle of treatment is that the photosensitizer enriched in the tumor site,which reacts with oxygen in the biological tissue under the irradiation of the appropriate wavelength light and produces reactive oxygen species to kill the tumor cells.Photodynamic therapy possesses a great deal of advantages comparing with traditional treatment,namely,broad anti-tumor spectrum,obvious light targeting and non-drug-resistance.But there is also a problem to be solved that the photosensitizer has insufficient uptake of target tissue.Compared with the neutral environment of normal cells,the microenvironment of the tumor site is acidic.Therefore,the design of pH-sensitive drug loading system is a significant strategy to improve drug targeting.Moreover,Coupling pharmacologically active domain with the photosensitizer is another strategy to improve the photosensitizer targeting since the small-molecule targeting drug can specifically recognize and kill the tumor cells.In this paper,two systems were designed and fabricated as ZIF-8 drug transport carrier with high drug loading and targeting and as UiO-66 system which used MOFs as the connecting unit to couple the small-molecule target drug and the photosensitizer molecule.And their targeting and photodynamic activity were evaluated based on the characteristics of ZIF-8 and UiO-66.The main research contents and achievements are as follows:(1)ZIF-8 @ Pc and ZIF-8 @ Pc + CTAB were prepared by loading the photosensitizer phthalocyanine(Pc)in ZIF-8 nanomaterials by one pot method.The structures were further characterized by XRD,SEM,TEM,IR,respectively.The results showed that ZIF-8 @ Pc and ZIF-8 @ Pc + CTAB all have good photodynamic activity,while the photodynamic power of the nanomaterials modified by CTAB performed more actively.In addition,photosensitizer molecules are mainly distributed in the lysosome of tumor cells.(2)Four kinds of nano-materials with different functional groups based on UiO-66 were synthesized by solvothermal method.After that,the target molecules and photosensitizer were coupled to UiO-66 by post-synthesis modification method to obtain five different functional of UiO-66 nanomaterials.The results showed that the introduction of phthalocyanine and erlotinib made UiO-66 had obvious photodynamic activity and higher tumor-targeting after characterizing their structures by XRD,SEM,TEM,IR and XPS and their cytotoxicity and evaluating their specificity to human hepatoma HepG2 cell,respectively.In summary,two drug-containing system based ZIF-8 and UiO-66 were prepared in this paper,which are expected to develop as highly efficient and low toxicity drug deliveries.