Ceria Based Nanozymes:Synthesis And Tumor Therapy Application

Cancer is one of the most death causing diseases,which poses a serious threat to human health.Traditional cancer treatment technology has many limitations and shortcomings,such as chemical treatment and radiotherapy have certain side effects,recurrence and metastasis after treatment is also a big problem,so it is necessary to develop new treatment technology to make up for the shortcomings of traditional treatment technology.Photothermal therapy driven by near-infrared light is a new type of tumor treatment technology with high attention.Its principle is to use the developed photothermal nano reagent to reach and gather at the tumor site through injection and other means,and then use the near-infrared laser to irradiate the tumor through the skin.Near infrared light has good skin penetration performance,the photothermal materials gathered in the tumor area generate heat by absorbing near-infrared light,and eventually increase the temperature inside the tumor to achieve the purpose of tumor cell ablation.At present,the most widely studied photothermal conversion materials include precious metals,organic polymers,semiconductor compounds and carbon-based nanomaterials.2,2’-Azinobis-（3-ethylbenzthiazoline-6-sulphonate）（ABTS）is often used as a chromogenic substrate for enzyme-linked immunosorbent assay（ELISA）.The substrate is catalytically oxidized to form ABTS free radical,which is a soluble green chelate and generates heat after absorbing near-infrared light.In this study,ABTS was loaded on the surface of CeO₂ nanoenzyme and injected into the tumor affected area.The weak acidity of tumor microenvironment and the high concentration of H₂O₂ were used to make ABTS only be catalysed and oxidized in the tumor affected area.Finally,the tumor area was heated by near-infrared light irradiation,resulting in tumor cell ablation.Because ABTS can only catalyze oxidation in tumor microenvironment,the normal tissues outside the tumor will not be heated by near-infrared light irradiation.Using this effect to improve the selectivity of hyperthermia,and finally realize the targeted treatment of tumor.The specific research work in this article is as follows:（1）CeO₂ nanoparticles with tubular structure were synthesized by a simple hydrothermal method using cerium chloride（CeCl₃·7H₂O）as cerium source.By adjusting the reactant concentration,pH value,temperature and reaction time in the reaction system,the obtained CeO₂ nanotubes have more uniform size distribution.The CeO₂ nanotubes were modified to disperse in aqueous solution.The performance of modified CeO₂ nanotubes was tested to explore the effects of temperature,substrate concentration,pH value and other factors on the performance of the enzyme,and to find the best conditions for catalytic reaction.（2）CeO₂ nanotubes were loaded with ABTS.The photothermal properties of CeO₂ nanotubes loaded with ABTS were systematically studied by simulating the cell environment,including the effects of hydrogen peroxide and pH value on the photothermal properties.In vitro cell experiment and in vivo mouse experiment further proved that CeO₂ nanotubes have potential application in photothermal tumor therapy.（3）Manganese dioxide was introduced to further improve the catalytic performance of the enzyme,and ceria based nanorods doped with manganese dioxide were obtained.The nanorods were optimized by controlling the reactant concentration,reaction time,reaction temperature and pH value of the reaction system.The surface of the prepared nanorods was modified and the enzyme performance was tested.The effects of system temperature,substrate concentration,pH value and other factors on the enzyme performance were explored,and the optimal conditions for catalytic reaction were found.The photodynamic therapy drug chlorin e6（Ce6）was loaded on the nanorods.The effect of photodynamic therapy was tested by cell experiment in vitro,and the photodynamic therapy experiment of mouse tumor in vivo confirmed that nanoenzyme could improve the effect of photodynamic therapy.In this study,we make full use of the unique catalytic performance of ceria based nanomaterials,aiming at improving the specific response of tumor photothermal therapy,we use the catalytic reaction of peroxidase to activate the photothermal performance of photosensitizer in situ in cancer cells,so that the drugs can be concentrated in tumor tissue to the maximum extent,and achieve efficient joint diagnosis and treatment based on the specific activation of tumor microenvironment.The design scheme proposed in this study is different from the simple superposition in the traditional design idea,which has certain uniqueness and pioneering,and provides a new research idea for the development and application of functional nano enzyme.