Study On Preparation Andantitumor Activity Of MOF@PPa/AF

Photodynamic Therapy(PDT),as a minimally invasive,small side effects,reproducible treatment,tumor specificity and low treatment cost,has been often used in combination with traditional methods in the treatment of tumor diseases in recent years.PDT mainly depends on oxygen,photosensitizer and light source,among which photosensitizer and oxygen affect PDT effect.However,in this study,magnesium pyrochlorophyll-a(PPa)was selected as a photosensitizer,which had strong hydrophobicity and poor water solubility,and was easy to accumulate in vivo to reduce the efficacy of PDT.Secondly,because PDT requires oxygen,the tumor microenvironment is hypoxic and PDT consumes oxygen,resulting in severe hypoxia in the tissue,which inhibits the treatment effect of PDT.In order to improve the biocompatibility of PPa,it is loaded on a nano-level MOF material with a large specific surface area and good porosity,so as to solve the problem that the photosensitizer is easy to self-polymerize and affect PDT.In addition to solve the treatment effect of severe tumor hypoxia limiting PDT,while introducing photosensitizers,6-aminoflavone(AF),a hypoxia-sensitive chemotherapy drug,was successfully loaded onto MOF by physical adsorption.Subsequently,the use of chemical modification to further polyethylene glycol(PEG),synthesis of biocompatibility,p H-responsive drug release PDT and hypoxia activated chemotherapy synergistically enhance the anti-tumor effect of multi-modal nano-platform Zr-MOF@PPa/AF@ PEG.The developed nanocomposite material has a high singlet oxygen yield and strong photobleaching resistance.PPa and AF were physically adsorbed to the pore and surface of MOF through hydrogen bonding,van der Waals force,π-π stacking,and the surface is modified with PEG to ensure the stable delivery of the drug in the body.The release rate of PPa and AF in the simulated micro-acid environment(p H=6.4)in vitro reached 68% and 78%,respectively at 12 hours,indicating that the tumor microenvironmental stimulus response has spatio-temporal selectivity.in vitro cell uptake is good,light stimulates cells to produce sufficient reactive oxygen species,and it has fluorescence imaging function.Zr-MOF@PPa/AF@PEG has excellent cytostatic effect by analyzing cell survival rate in vitro,which can be directly proved by AM-PI cell staining experiment.In vivo anti-tumor experiments show that Zr-MOF@PPa/AF@PEG has a significant inhibitory effect on tumor-bearing mice,which is more effective than Zr-MOF and Zr-MOF@PPa@PEG.The pathological sections of the Zr-MOF@PPa/AF@PEG group showed that the tumor sections of the tumor-bearing mice showed a large degree of tissue necrosis-like changes and compared with the single Zr-MOF@PPa@PEG,the degree of necrosis was significantly increased.The above results all indicate that PDT combined with hypoxia-activated chemotherapy enhances the anti-tumor ability.there is no obvious pathological damage in the histopathological sections of all organs,indicating that there are no obvious side effects at the current dose of Zr-MOF@PPa/AF@PEG that does not affect the normal function of the main organs,and can be used safely and effectively.therefore,the strategy based on PDT that induces tumor hypoxia and activates sensitive chemotherapeutics to enhance the anti-cancer effect is an effective way to solve the problem of PDT in the treatment of hypoxia.The composite nano-platform developed in this article is expected to become a new high-efficiency multi-modal cancer treatment method.