Applications Of Iron Phosphate Redox Nanozyme In Tumor Oxidative Stress Therapy

In recent years,nanoenzyme have gradually emerged and received widespread attention.Nanozyme have similar catalytic activities as natural enzymes,and overcome the shortcomings of natural enzymes such as easy inactivation and low yield.Moreover,multi-enzyme activity can be achieved by changing the structure,size,surface modification,recombination.The discovery of iron oxide nanozymes has created a new era of inorganic nanomaterials as mimicking enzymes.Researchers have successively discovered that metal oxides,noble metals,carbon-based nanomaterials,etc..They have various redox activities,including superoxide dismutase?SOD?,oxidase?OXD?,catalase?CAT?,peroxidase?POD?.A large number of reports have reported that iron-based nanomaterials have a wide range of applications in the biomedical field.Hydrogen peroxide converts into hydroxyl radicals through iron ion-mediated Fenton reaction,which exhibits extremely strong oxidizing properties.In this study,the classical hydrothermal method was used to prepare iron phosphate nanozyme?FePOs?using iron salt and phosphoric acid as raw materials,sodium lauryl sulfate as a capping agent and urea as a precipitant.The composition,morphology and structure were characterized by EDS,TEM and X-ray light scattering.FePOs nanozymes were prepared by controlling the experimental conditions as follows:the molar ratio of Fe₂?SO₄?₃ to H₃PO₄ was 1:2,the reaction temperature was140°C,and the reaction time was 2 h.The as-prepared FePOs was noncrystalline sphere-like particles with an average diameter of 420⁴30 nm.The percentage of iron elements is 44.38 wt.%.TMB colorimetric method and oxygen generation methods were used to identify the peroxide-like and CAT-like activities of the FePOs,respectively.The results indicated that the prepared FePOs exhibited peroxidase-like activities at lower pH conditions and could accelerate the redox reaction of TMB-H₂O₂ system as natural peroxidase.At near neutral pH conditions,the FePOs could catalyze O₂ generation from H₂O₂ as natural CAT.In cell experiments,no significant cytotoxicity of various cells was observed after incubation with FePOs for 24 h.The catalytic effect of the FePOs was remarkable in the prensence of safe dose of H₂O₂,which promoted the conversion of H₂O₂ to·OH and showed strong oxidative effect and irreversible damage to cell mitochondria and DNA in the form of significant decrease of mitochondrial membrance potential and DNA damage.In animal experiments,the 4T1-Luc subcutaneous xenograft model was constructed by inoculating the rice-tumor under the skin.The tumor inhibition experiment was performed when the tumor volume grew up to 200 mm³.The experimental results showed that the FePOs nanozymes inhibited the growth of tumors as soon as they were in situ injected into the tumors.The reason could be ascribed to the acidic environment and higher H₂O₂ level in tumor tissues than normal tissues.Then a great number of·OH radicals were generated from endogenous H₂O₂,which was catalyzed by the injected FePOs,and killed the cancer cells in a short time.The anti-tumor efficiency was further enhanced to as high as 84.4%with the addition of exogenous H₂O₂.