Cascade Catalytic Reaction Of Iron Oxide Nanoparticles And Its Preliminary Application

The fast development of biomedicine has been beneficial to the deep understanding of cancer-associated biology.As an important part of tumor tissue,the tumor micro-environment(TME)plays indispensable role in in determining the development and progression of the tumor.Characterized by mild acidity(low p H),H₂O₂ overproduction and hypoxia,TME not only provides a suitable environment and nutrition for tumour development and metastasis but also furnishes the“gate”for selective and efficient tumour treatments.In this case,nanocatalysts,such as Ti O₂,Ce O₂,and Mn O₂ nanoparticles,have been designed with unique responsiveness toward TME stimuli to initiate catalytic reactions and modulate biological microenvironments for eliciting therapeutic effects in recent decades.Among them,the nanomaterial(Fe₃O₄)with Fenton catalytic properities can react with H₂O₂and produce highly biotoxic reactive oxygen·OH under the stimulation of tumor microacidity and high concentration of H₂O₂,playing an anticancer role.Thus,this paper combined Fe₃O₄with glucose oxidase(GOx)to design two kinds of nanoparticles with TME-induced cascade catalysis,and explored its potential applications in tumor nanocatalysis therapy brefly.The study could be divided into the following three parts:(1)The preparation and characterization of Fe₃O₄/GOx-PLGA nanoparticles.Fe₃O₄-OA NPs(15 nm)modified by oleic acid were prepared by chemical co-precipitation method,and then encapsulated in PLGA polymer microspheres modified with Pluronic F127 by emulsification-solvent volatilization technology.Fe₃O₄/GOx-PLGA NPs(270 nm)were obtained after loading GOx.The prepared Fe₃O₄/GOx-PLGA NPs have an uniform morphology,narrow particle size distribution(PDI 0.217),as well as good stability and dispersibility in aqueous solution(?=26.7 m V).(2)Preliminary exploration of the potential CDT properties of Fe₃O₄/GOx-PLGA nanoparticles.In glucose-rich acidic environment,the GOx in Fe₃O₄/GOx-PLGA NPs could effectively deplete the glucose nutrients by an enzyme-catalyzed bioreaction,which also in situ generates abundant H₂O₂ molecules.The elevated H₂O₂,could be further catalyzed to produce large amounts of hydroxyl radicals by the co-encapsulated Fe₃O₄NPs in Fe₃O₄/GOx-PLGA NPs via a Fenton-like reaction.Based on this unique cascade catalytic property,Fe₃O₄/GOx-PLGA NPs can be used as a potential nano-drug to convert endogenous glucose into highly biotoxic·OH in the acidic environment of tumor,and inhibited tumor growth through the synergistic effect of starvation therapy and chemodynamic therapy.In this paper,the catalytic performance of Fe₃O₄/GOx-PLGA NPs was evaluated by a colorimetric experiment,and the steady-state kinetic constant K_M=48.76 m M and the maximum catalytic rate V_max=1.12×10^-7 M/s of Fe₃O₄-PLGA NPs related to H₂O₂were obtained.It has been found that cell viabilities are highly dependent on the dosage of Fe₃O₄/GOx-PLGA NPs and p H value of the medium,which imply that Fe₃O₄/GOx-PLGA NPs can induce oxidative stress and effectively inhibit the growth of tumor cells in a glucose-rich acidic environment,and it is expected to be used as bio-catalytic reagent in the field of tumor treatment.(3)The preparation and catalytic activity of Fe₃O₄@Mn O₂/GOx nanoparticles.Fe₃O₄ NPs with uniform particle size and good monodispersity was prepared by a solvothermal reaction.Subsequently,flower-shaped Fe₃O₄@Mn O₂NPs was obtained through further hydrothermal reduction reaction.Moreover,the multi-functional catalytic material-Fe₃O₄@Mn O₂/GOx NPs was successfully constructed by loading GOx with physical adsorption.The combination of Fe₃O₄ NPs and GOx endowed Fe₃O₄@Mn O₂/GOx the cascade catalytic properties of tumor microenvironment response.Moreover,Mn O₂ component can consume glutathione(GSH)in tumor tissues and promote the increase of effective concentration of·OH in cascade catalytic reaction.After endocytosis by tumor cells,the over production of H₂O₂ allows for decomposition of Mn O₂ shell,triggering the generation of O₂ effectively for subsequent catalytic reaction.In this paper,these multifunctional catalytic activities were evaluated in vitro colorimetric experiments.Based on the combination of GSH consumption and GOx Fe₃O₄ cascade catalytic properties,Fe₃O₄@Mn O₂/GOx was expected to improve the yield of·OH in chemodynamic therapy(CDT),thus improvimg the treatment effect of CDT.