Construction Of Transition Metal Compounds-based Composites For Anti-cancer Therapy And Imaging

Cancer,as one of the most deadly diseases in the world,remains a serious threat to human health.In recent years,despite enormous reseach in nanotechnology and nanomaterials to develop anti-cancer treatment,only limited success has been achieved due to poor solubility,low biosecurity and lack of drug released specificity.In addition,it is difficult for a single treatment modality to eliminate the whole tumor and prevent cancer metastasis.Nanotechnology and nanobased drugs with.the capability of diagnosis and therapy have attracted wide attention.Compared to conventional anti-cancer drugs,novel nanocomposites have allowed for the possibility of assembling several types of diagnostic and therapeutic agents into one nanostructure through physical adsorption and chemical binding forces,realizing the integration of multimode imaging including fluorescence imaging,computed tomography,magnetic resonance imaging and photoacoustic imaging with multifunctional therapies such as photothermal therapy,photodynamic therapy and chemotherapy.In the reseach of this paper,we constructed trasition metal compounds-based nanocomposites to combine diagonosis with therapeutics and revealed the biosecurity and anti-cancer treatment effect.The morphology and structure of the materials are analyzed in detail by XRD,TEM and FT-IR.And the cytotoxicity,mechanism and principle of anticancer therapy were explored though the experiments in vivo and vitro.The main contents of this paper are given as follows:CuS nanoparticles with the size of 8 nm were prepared.After modified by amino,CuS nanoparticles were conjugated with Pt(?)prodrugs.Finally,CuS-Pt(?)nanoparticles were obtained after conjugated with folic acid(FA)for and polyethylene glycol(PEG).Pt(?)prodrugs could be reduced to more toxic Pt(?)by abundant glutathione in the tumor microenvironment.We explored the promotion mechanism for enhancing chemotherapy effect.Fluorescein isothiocyanate(FITC)modified CuS-Pt(?)nanoparticles could be used as probes for fluorescence imaging.And the targeting ability of FA was revealed by CLSM.Based on experiment results,CuS-Pt(?)nanoparticles combined photothermal therapy with chemotherapy could inhibit tumor growth obviously.Meanwhile,hyperthermia could accelerate the release of Pt(?)prodrugsSubsize MnO2 nanosheets were acquired from bulk MnO2 by ultrasonication.After modification by animo,Au25 clusters and Pt(?)prodrugs were wrapped on the surface of MnO2 nanosheets to obtain biodegradable MnO2-Pt@Au25.The biodegradation condition of MnO2 nano sheets in the tumor microenvironment were observed by UV-vis spectra and bio-TEM.And the roles of biodegradable MnO2-Pt@Au25 were explored:(1)On account of superfluous H2O2 and glutathione in the acidic tumor microenvironment,MnO2 nanosheets can be reduced to generate a great amount of O2.The consumption of singlet oxygen(1O2)was decreased,and the efficiency of enhancing photodynamic therapy was further studied.(2)Mn2+,as the reaction product,can be employed as contrast agents for magnetic resonance imaging.The results in vivo and in vitro revealed that we engineered a kind of tumor microenvironment responsive system for fluorescence/magnetic resonance imaging guided synergistic therapy.Pt(?)prodrugs play the role as a bridge in linking NaGdF4:Yb/Tm@NaGdF4:Yb(UCNPs)modified by polyetherimide and ZnFe2O4 modified by dopamine to obtain size-tunable UCPZ-PEG.After phagocytosis by cancer cells,the "bridge" broke due to the reduction reaction between Pt(?)prodrugs and glutathione,realizing size change of nanocomposites.And assess the effect of promoting deep tumor penetration,distribution,and cytotoxicity.The size change of UCPZ-PEG and Fenton reaction were demonstated by TEM and XPS.More researches were carried out about the nanocomposites used as the contrast agents of multifarious bioimaging technologies,including computed tomography,upconversion luminescence,magnetic resonance and photoacoustic tomography imaging.After ultrasonication,ultrathin graphene oxide(GO)nanosheets were obtained from GO sheets prepared according to Hummers.ZnFe2O4 nanoparticles were anchored on GO nanosheets uniformly by hydrothermal process.Notably,we transferred NaGdF4:Yb,Tm(upconversion nanoparticles,UCNPs)from oil phase to water phase and easily grafted them with GO/ZnFe2O4 nanosheets to acquire GO/ZnFe2O4/UCNPs-PEG.Tm3+-doped UCNPs can emit UV-visible light under 980 nm laser exciting,which could be used as UV light source to trigger the photodynamic therapy effect and Fenton reaction of ZnFe2O4.In addition,980 nm laser could trigger the dual-photothermal effect of GO and ZnFe2O4.The UCNPs doped with Gd3+ and Yb3+ can act as nanoprobes for computed tomography/upcolversion luminescence imaging,and ZnFe2O4 can be used as T2-weighted contrast agent of magnetic resonance imaging.After modified by near-infrared fluorescent dyes(IR783),the nanocomposites could be used for photoacoustic tomography.The system achieved four-model imaging-guided high-efficiency dual-phototherapy.