(Quasi) Electron Transfer Properties Of Inorganic Functional Materials For Disease Treatment

Electron transfer phenomenon exists widely in physics,chemistry,biomedicine and material science.Among them,（quasi）electron transfer reactions play an essential role in human health.Generally speaking,highly ordered（quasi）electron transfer reactions are the essence of the organism to steadily achieve specific biological functions.Once these specific electron transfer reactions were destroyed,it would easily affect the normal functions of the body and cause a series of diseases.Therefore,precise regulation of key electron transfer reactions to disrupt or reshape specific biological functions of the body is expected to provide inspirations for the treatment of refractory diseases.It is worth mentioning that nanomaterials have unique physical and chemical effects and have rich structural and functional design.Therefore,it is of great exploration value to achieve precise regulation of specific（class）electron transfer reactions by biomedical nanomaterials.Briefly,this thesis focused on the precise control of（quasi）electron transfer reactions under complex physiological conditions.We designed and synthesized a series of nanodrugs with（quasi）electron transfer properties for the key components of the lesion area,and systematically explored the ability of this kind of nanodrugs to interrupt,reshape or regulate the biological functions of the body,so as to realize the treatment of refractory diseases.It mainly includes the following aspects:1.Reductive stannic oxide-based electron transfer property interrupts endoplasmic reticulum function for cancer therapy.Oxidative damage is thought to be the main mechanism of most tumor treatments.However,the endoplasmic reticulum（ER）of cancer cells can form the antioxidant defense system by synthesizing a series of enzyme-based antioxidants,which seriously weakens the anti-cancer effect of oxidative damage mechanism.In order to solve this bottleneck problem,an innovative strategy of reductive damage-related“electronic interference therapy”was proposed for the first time in this chapter.The novel electron donor（UCSNK）with near-infrared light（NIR）triggered and ER targeting function was obtained by in situ loading of reductive stannic oxide(Sn O_2-x)onto the surface of upconversion luminescent nanoparticles coated with silicon oxide（UCNPs@Si O₂）,and modifying the ER retention signal polypeptide KDEL with its outer layer.After entering the tumor cells,the UCSNK NPs target the ER.The generated ultraviolet（UV）fluorescence from the UCNPs under NIR irradiation excites the separation of electron-hole pairs in the Sn O_2-x shell,and oxygen vacancies of Sn O_2-x can serve as effective sacrificial electron donors to scavenge the photogenerated holes.Thus,the surviving photogenerated electrons disrupt the oxidative microenvironment of ER by means of reductive damage,destroy the homeostasis of ER protein folding function,and eventually lead to apoptosis of cancer cells.In vitro and in vivo experimental results revealed that this photo-induced electron transfer process significantly increased the reducing equivalent level in the ER region,achieving efficient treatment of tumors.It is worth mentioning that for the first time,photo-induced electrons transfer to disulfide bonds were accurately detected at the molecular and protein levels using transient absorption spectroscopy.In this chapter,this reductive damage-related“electronic interference therapy”is proposed to use photogenerated electrons to interfere with the key electron transfer reaction of protein disulfide bonds formation in ER,and ultimately induces tumor death through reductive damage,which provides a new idea for the novel cancer therapy and the cross fusion of electronic biology and biomedical science.2.Magnesium boride-based quasi-electron transfer property reshapes self-healing function for wound treatment.Different from tumor treatment strategies that interrupt the biological functions of cancer cells,reshaping the biological functions of wound is the core of wound healing strategies.However,due to the complex biological effects of the carbohydrate components,uncontrollable biological functions usually occur in the self-healing process of wound.Boron dihydroxyl groups,as the classical functional group of carbohydrates-responsive material system,are able to complex with carbohydrates to form borate ester bonds.However,these dynamic covalent bonds are difficult to exist under physiological conditions.In order to solve this bottleneck problem,a novel“carbohydrates complex device”magnesium boride（MB NPs）was designed and synthesized by high temperature self-propagating combustion method.In the process of MB NPs hydrolysis,boron dihydroxyl groups with sp³ configuration are formed,which increase the reaction rate of complex with carbohydrates.In addition,the hyperconjugation effect of the two-dimensional hydrolysates promotes electron migration to the borate ester bonds by means of quasi-electron transfer,which greatly improves the stability of the borate ester bonds.In the diabetic wound model（carbohydrates played a negative role）,MB NPs reduced the blood glucose concentration and reshaped the self-healing function of the diabetic wound by inhibiting the key electron transfer reaction of protein glycosylation.In the acute gastric ulcer model（carbohydrates played a positive effect）,MB NPs and gelatinized starch were blended into glue,which effectively adhered to gastric wounds,blocked further erosion of gastric juice,and reshaped the wound self-repair function of gastric wall.The“carbohydrates complex device”proposed in this chapter utilizes the quasi-electron transfer properties of MB NPs to improve the ability of carbohydrates complexing,thus reshaping the self-healing function of carbohydrates-related wounds,which has essential basic research significance and potential clinical transformation value.3.Metal boride-based quasi-electron transfer property to regulate the microenvironment of skin lesions for skin infection treatment.As a skin disease with more complex pathological microenvironment,the conventional treatment strategy of skin infection focuses on sterilization,while it is difficult to reshape the self-healing function of the infected skin.Lipopolysaccharides（LPS）are key components of both bacterial cell walls and dead bacteria that release endotoxins,and are essential for maintaining bacterial survival and inducing excessive inflammation.Therefore,how to specifically and continuously block the biological activity of LPS is essential for sterilization and inhibition of excessive inflammation.To solve this bottleneck problem,the“key component capture”strategy was proposed in this chapter.A series of nanoscale reactive metal borides（M_xB_y NPs,M=Mg,Al and Be）were designed and synthesized by high temperature self-propagating combustion method.M_xB_y NPs slowly hydrolyze in skin lesions to generate boron dihydroxyl groups and metal cations,which promote the local microenvironment to be transformed into an alkaline microenvironment with antioxidant capacity.The hydrolyzed products of M_xB_y NPs have quasi-electron transfer properties and significantly improve the“capture”ability to LPS.This feature not only interferes with the biological function of LPS in maintaining bacterial cell wall structure and enhances the antibacterial effect of metal ions,but also effectively inhibits the key electron transfer reaction of LPS-induced phosphorylation of MAPK signaling pathway protein and efficiently blocks the excessive inflammatory reaction caused by endotoxin.The in vitro antibacterial experiments and in vivo skin infection experiments showed that M_xB_y NPs had excellent anti-infection ability and skin infection repairing effect.This“key components capture”strategy proposed in this chapter utilizes the quasi-electron transfer properties of M_xB_y NPs to capture key components of bacteria and achieve the regulation of specific biological functions in the complex pathological microenvironment,which is expected to provide inspirations for the treatment of complex skin diseases.