Study On The Clearance Of Inflammation/Reactive Oxygen Species By Prussian Blue Nanoparticles And Its Related Mechanism

Objective: Inflammatory and excessive reactive oxygen species(ROS)plays a key role in the occurrence and development of many diseases.The main purpose of this paper is to explore the application and related mechanism of Prussian blue nanoparticles(PB)with good biocompatibility and biosafety in inhibiting inflammation / scavenging active oxygen.The main work is divided into two parts: 1)Prussian blue nanoparticles in the treatment of acute pancreatitis(AP)and its mechanism;2)Prussian blue nanoparticles self-synergistic effect:efficient photothermal treatment of tumors and reduce the side effects of photothermal therapy(inflammation and reactive oxygen species induced by photothermal therapy).Methods: 1)Prussian blue nanoparticles were prepared by PVP modification method.Its physical and chemical properties in vitro were verified by transmission electron microscopy(TEM),ultraviolet-visible light-near infrared(UV-vis-NIR)and other physical characterization.Its catalytic ability of scavenging ROS in vitro was detected.The biological safety of PB was evaluated by cytotoxicity test,and the effect of PB on inhibiting inflammation and scavenging ROS was verified at the cellular level.The efficacy and mechanism of PB in the treatment of acute pancreatitis were evaluated by serum test in vivo,histological score of H&E staining,TUNEL fluorescence staining,PCR ARRAY and gene thermography,and KEGG analysis.2)Prussian blue nanoparticles with single composition and good biocompatibility were prepared by optimizing material ratio.The successful preparation of PB was proved by the characterization of the materials in vitro.808 nm near infrared laser and infrared thermal imaging were used to explore the photothermal effect of PB,and electron spin resonance(ESR)was used to detect the ROS scavenging ability of PB.The ability of PB to inhibit inflammation and clear ROS was verified at cell level.The process of phagocytosis of PB by breast cancer cells and the photothermal killing effect of PB on breast cancer cells were observed by laser confocal microscope.In vivo serum biochemistry,blood routine,liver and spleen immune cells were detected,and TUNEL staining was used to detect the biosafety of PB in vivo.In the animal experiment,the subcutaneous tumor model of breast cancer mice was established,the therapeutic effects of photothermal therapy on breast cancer in different experimental groups were compared,and the levels of serum inflammatory factors and ROS around the tumor tissue were measured to evaluate the side effects of photothermal therapy while reducing the side effects of photothermal therapy(inflammation around the tumor induced by photothermal ablation and ROS).At the same time,the therapeutic effect of PB in photothermal therapy of breast cancer was evaluated by ultrasound,contrast-enhanced photoacoustic imaging,infrared thermal imaging and laser confocal imaging.And through serum detection,H&E evaluation,tumor volume monitoring before and after treatment to comprehensively evaluate the efficiency of PB photothermal treatment of tumors and reduce the side effects of photothermal therapy,self-synergistic and efficient treatment of tumors.Results: Prussian blue nanoparticles were successfully prepared.The materials were uniformly dispersed and the particle size was about110 nm.UV-vis-NIR spectrum analysis shows that PB has a strong absorption peak in the near infrared region,which ensures the good photothermal conversion efficiency of PB.The catalytic experiment in vitro proved that PB could efficiently remove ROS.The cell level showed that PB could inhibit the release of inflammatory cytokines and had the ability of scavenging ROS.In vivo experiments,PB showed strong antioxidant and anti-inflammatory effects in the treatment of acute pancreatitis in vivo and in vitro,which could reduce oxidative stress and reduce inflammatory reaction.The therapeutic effect of PB on AP may be related to the inhibition of Toll-like receptor / nuclear factor(NF)-κ B signal pathway and the scavenging of reactive oxygen species.PB in the animal model of breast cancer,PB can efficiently kill the tumor,inhibit the inflammation induced by photothermal process and eliminate the production of excessive ROS,and exert the self-synergistic effect of "photothermal-anti-inflammatory" and "photothermal-anti-ROS" to treat tumor.Conclusion: Prussian blue nanoparticles,which can effectively inhibit inflammation / scavenge reactive oxygen species,can treat acute pancreatitis by inhibiting the inflammation and ROS signaling pathway of Toll-like receptor / nuclear factor NF-κB.Prussian blue nanoparticles have high photothermal conversion efficiency and can effectively kill tumors by reducing inflammation and excessive ROS induced by photothermal therapy.