Prussian Blue Based Nano-system For Drug Delivery And Application In Tumor Photothermal-Chemotherapy

Prussian Blue is a clinical drug approved by the US Food and Drug Administration(FDA)for the treatment of radiation-induced diseases of thallium and cesium,indicating its biosafety.In recent years,based on its good biocompatibility,unique metal organic framework(MOF)structure,strong absorption in the near-infrared region and excellent photothermal conversion efficiency,Prussian Blue nanoparticles(PB NPs)have been developed as a new generation of tumor photothermal therapeutic agents and a drug carrier.However,its application is limited by the lack of targeting of the tumor and the controlled release of the loaded drug.In this paper,based on the different morphology of the thermal performance of the PB,use of red cell membrane package nano materials to enhance their ability of immune evasion and modification,and preparation of Prussian Blue nano-bionic composite material loaded with chemotherapeutic drug doxorubicin(DOX).It is also used in the treatment of cervical cancer with photothermal-chemotherapy,and has achieved good application results.This nano-composite material achieves precise and controllable release of chemotherapeutic drugs and has a good application prospect in the field of targeted drug delivery.Following are the main research contents:1.Development of Prussian Blue nano-targeted drug delivery system and characterization of drug loading performanceBy controlling the feed ratios of potassium ferricyanide,polyvinylpyrrolidone and hydrochloric acid,the spheric and cubic PB nanoparticles with hollow mesopores can be controlled and synthesized,and the mass ratio of spheric and cubic PB can be further investigated by photothermal effect screening.The ratio of 1:1 was the best PB combination.The PB combination had a DOX loading rate of up to 130% and was encapsulated by erythrocyte membrane to form a core-shell structure SCPB@DOX@EM.Finally,it was modified by phospholipid PEG and grafted to the target molecule folic acid(FA)to finally obtain a target drug loading system SCPB@DOX@EM@FA.The successful synthesis of spheric and cubic hollow mesoporous PB was characterized by transmission electron mi croscopy,scanning electron microscopy,Zeta particle size and nitrogen adsorption.The UV-visible spectrum,potential analysis and fourier transform infrared spectroscopy were used to characterize the successful construction of the drug system SCPB@DOX@EM @FA.In vitro photothermal experiments,hemolysis experiments and macrophage phagocytosis experiments showed that SCPB@DOX@EM@FA had excellent photothermal conversion capability and photothermal stability,and good Biocompatibility and strong immune evasion.2.Prussian Blue nano-targeted drug delivery system for photothermal-chemotherapy combination therapy for cervical cancerThe Prussian Blue nano-targeted drug delivery system SCPB@DOX@EM@FA extended the circulation time in the blood by EM camouflaging,which enabled the continuous accumulation of nanocomposites at the tumor site.In vitro anti-tumor experiments showed that the drug-loading system had a combined therapeutic effect of photothermal-chemotherapy on HeLa cells,and the killing ability was reached more than 96 %.In vivo anti-tumor experiments,SCPB@DOX@EM@FA was injected into HeLa tumor-bearing mice through the tail vein,and the tumor targeting ability of SCPB@DOX@EM@FA was verified by a living imager and a thermal infrared imaging system.After 16 days,the tumor inhibition rate(TGI)of the mice was as high as 99.6 %.Other physiological indexes of the mice showed that SCPB@DOX@EM@FA was a safe,non-side-effect nano-photothermal-chemotherapy preparation.