A Case Study On The Synthesis, Structure And Antitumor Application Of A High Nuclear Polymolybdate Cluster

The heterogeneity and complexity of cancer make it one of the important threats to people's health.To mitigate the threat of cancer,researchers around the world have been working hard to develop more effective treatments to fight cancer.Nanozymes,as a new enzyme therapy for cancer treatment,have attracted widespread attention from researchers.Nanozymes are a class of inorganic nanoparticle catalysts with enzyme-like activity,which can use metabolites(hydrogen peroxide,glutathione,glucose,and oxygen etc.)in tumors as substrates to change the state of reactive oxygen species under the catalysis of nanozymes,thereby disrupting the intratumoral redox balance.Nanozymes such as peroxidase,oxidase,and glucose oxidase,which can act as oxidants,have the potential to achieve more effective and safe cancer therapy.Polyoxometalates(POMs)are a class of transition metal(Mo,W,Ti,V,Nb,etc.)oxygen clusters with rich structure,excellent redox performance,and semiconductor characteristics.Since polyoxometalates have rich and diverse structures,nano-scale sizes,redox properties,and have the characteristics of adjustable particle size,composition,and charge,they have been widely studied in the field of tumor metal drugs.In addition,the Bronsted acidity and oxidative properties of POMs themselves also promote their application in the field of nanozymes.Based on this,this thesis,relying on the nano-sized mixed-valence high-nuclearity polymolybdate cluster Mo₂₄₀ prepared by the research group,has carried out research on its application as a nano-enzyme in tumor treatment,which can be divided into the following contents:Firstly,the synthesis of Mo₂₄₀ had been extensively explored by changing conditions such as molybdenum salt,sulfate,reducing agent,acid,reaction temperature,reaction time,system p H,etc.By judging the crystal size,crystal form,crystal yield,and impurities,the optimal scheme for the synthesis of Mo₂₄₀ was optimized.Then through a series of characterization methods such as X-ray powder diffraction(PXRD),element mapping,Raman spectroscopy,infrared spectroscopy(IR),X-ray photoelectron spectroscopy(XPS),thermogravimetric analysis(TGA),and water vapor adsorption test,the basic properties of Mo₂₄₀ were characterized.Next,the tetra-n-butylammonium salt of Mo₂₄₀(denoted as TBA-1)was prepared.STEM,TEM,Raman spectroscopy,and ultraviolet spectroscopy were used to prove that Mo₂₄₀ has good stability in H₂O and acetonitrile solutions.Then,a series of solution experiments confirmed that Mo₂₄₀ has three enzyme mimic activities.Firstly,Mo₂₄₀ has peroxidase-mimic activity,which can catalyze the generation of highly toxic hydroxyl radicals(·OH)from H₂O₂.Secondly,Mo₂₄₀ can simulate catalase,which can decompose H₂O₂ to generate O₂ and H₂O.Finally,the O₂decomposed by the catalase-mimic enzyme of Mo₂₄₀ can be further catalyzed into the toxic substance superoxide anion(O₂^·-)through the oxidase-mimic activity of Mo₂₄₀.In addition,Mo₂₄₀ can also drive the Russell mechanism to catalyze the decomposition of hydrogen peroxide to singlet oxygen(¹O₂).Mo₂₄₀ degrades rapidly in a physiological environment(p H?7.4),but in a simulated tumor microenvironment,the degradation rate is slowed down and the structure is maintained for a longer time,which can reduce damage to normal cells.Finally,a series of cell experiments were designed for Mo₂₄₀ to further prove it in vitro.After studying the cellular uptake of Mo₂₄₀,we screened seven different cancer cell lines(human liver cancer cells(Hep G2 and SSMC-7721),human cervical cancer cells(He La),melanoma cells(B16F10),human ovarian cancer cells(SKOV3),mouse breast cancer cells(4T1),mouse colon cancer cells(CT26)and calculated the corresponding IC₅₀ values.It was finally screened out that Mo₂₄₀ has the strongest inhibitory effect on He La cells proliferation.After that,specific indicators were selected for different products,and qualitative and quantitative verification of the properties of various simulated enzymes were carried out at the cellular level.Finally,a series of preliminary biomedical experiments were conducted to investigate the therapeutic effect of Mo₂₄₀ nanozyme on tumor cells,and it was concluded that Mo₂₄₀inhibited the proliferation of He La cells through apoptosis.In general,Mo₂₄₀ can act as an effective redox balance disruptor.Mo₂₄₀ nanozymes can kill tumor cells by catalyzing reactions to generate various ROS(·OH,O₂^·-and ¹O₂),thereby realizing efficient catalytic therapy.