Preparation Of Ultrasound-responsive Catalytic Microbubbles And Their Application In Dental Whitening And Biofilm Removal

In recent years,nanocatalytic therapy based on nanozymes has shown promising applications.Nanozyme has similar catalytic activity as natural enzymes and has the advantages of low cost,stability,and easy regulation.Some nanozymes with peroxidase-like activity can convert H₂O₂ into hydroxyl radicals（·OH）,which can be used to treat tumors,infections,and other diseases by disrupting the structure and function of cells.However,nanocatalytic therapy still suffers from low catalytic efficiency,poor penetration,and lack of selectivity.Therefore,it is important to develop efficient and controllable catalytic systems.Ultrasound-responsive microbubbles（MB）are a class of materials with dimensions of 1-10μm,which compose of lipids,proteins,polymers and others wrapped gas nuclei.MB can exhibit unique properties,including contraction,oscillation,expansion,and rupture,under the stimulation of ultrasound,generate mechanical effects such as microjets and shear forces,and effectively enhance the penetration of loaded drugs,which makes them an efficient drug delivery platform.Meanwhile,ultrasound has high penetration and low damage to human tissues,which is more suitable for biomedical applications compared to light and microwaves.Therefore,nanozymes-functionalized MB with both catalytic properties and ultrasound responsiveness can enhance the catalytic activity of nanozymes by using external physical stimuli,overcome the biological barriers for nanozymes penetration,and improve the controllability of treatment,thus developing a new type of highly efficient catalytic treatment system.Based on the above background,we constructed two ultrasonically responsive catalytic microbubbles for the synergistic physicochemical treatment of dental whihtening and biofilm removal.The main contents of this thesis are as follows.1.Preparation of Fe₃O₄ catalytic microbubbles and tooth whitening studyTraditional tooth whitening methods often use highly concentrated H₂O₂ solutions,which are inefficient in degrading organic chromogens on the tooth surface and have significant side effects.Therefore,it is important to develop highly efficient and controllable tooth whitening reagents.In this study,catalytic microbubbles based on Fe₃O₄ nanozymes were constructed and their tooth whitening performance was investigated.First,Fe₃O₄ nanoparticles（Fe₃O₄ NPs）were combined with sodium dodecyl sulfate（SDS）to prepare Fe₃O₄ microbubbles（MB）by self-assembly.Then,the physical,chemical,and biological properties of the materials,such as morphology,structure,ultrasonic responsiveness,enzyme-like activity,and cytotoxicity of MB,were investigated.The experimental results showed that MB have peroxidase-like activity,which can convert H₂O₂ to·OH and further enhance the catalytic performance under ultrasound to degrade the chromogen attached on teeth and improve the whiteness of teeth.To verify its practicality,we prepared ultrasound-responsive tooth whitening gels by adding MB and H₂O₂ into carbomer gels,which can effectively whiten teeth with the presence of 6%H₂O₂ and ultrasound.2.Ultrasonic/magnetic field dual-responsive catalytic microbubbles for bacterial biofilm removalBacterial biofilm infections are difficult to treat with antibiotics and are therefore a serious risk to human health.Biofilms act as a barrier,preventing the penetration of therapeutic agents and protecting the bacteria within the biofilm.Therefore,disrupting the biofilm barrier is the key to effective removal of bacterial biofilm.To address these issues,a hybrid microbubble based on Fe₃O₄NPs and glucose oxidase was constructed to enhance biofilm destruction by using the mechanical force of ultrasound and magnetic field,and then further remove the biofilm by using the catalytic property of microbubbles.First,GOx-functionalized microbubbles（MBG）were prepared by self-assembling the composites of Fe₃O₄ NPs,SDS,and glucose oxidase（GOx）;then,MBG were characterized in terms of morphology,structure,ultrasonic response properties,enzyme-like activity,cascade catalysis,and cytotoxicity.The experimental results showed that MBG have ultrasound/magnetic field dual response properties.Under the effect of ultrasound stimulation and vibrating magnetic field,MBG can destroy the biofilm structure by mechanical action,which facilitates the penetration of other therapeutic reagents;meanwhile,GOx can convert glucose in the environment to H₂O₂ and further be converted to·OH by Fe₃O₄ NPs,thus killing bacteria in the biofilm.