Mutifunctional Photothermal Nanoagents For Tumor Mutimodel Imaging And Phototherapy

With the development of nanomedicine,the application of nanoparticles in cancer theranostics has attracted gtreat attention.Integrating diagnostic and therapeutic functions in one single nanostructure to develop theranostic platform has attracted intense attention in the personalized nanomedicine and clinical application.Among them,photothermal transduction nanomaterials hold great potential for nanomedicine.In this dissertation,four kinds of multifunctional photothermal nanoagents have been designed and fabricated for tumor multimodel imaging and phototherapy.1.A sort of porphyrin derivatives(P)with high singlet oxygen generation ability was sythesised.The P was conjugated to polyethylene glycol(PEG)ylated and aptamer-functionalized graphene quantum dots(GQDs)to gain a multifunctional theranostic agent(GQD-PEG-P).The resulting GQD-PEG-P displayed good physiological stability,excellent biocompatibility and low cytotoxicity.The intrinsic fluorescence of the GQDs could be used to discriminate cancer cells from somatic cells,while the large surface facilitated gene delivery for intracellular cancer-related microRNA(miRNA)detection.Importantly,it displayed a photothermal conversion efficiency(PCE)of 28.58%and a high quantum yield of singlet oxygen generation up to 1.08,which enabled it to accomplish advanced photothermal therapy(PTT)and efficient photodynamic therapy(PDT)for cancer treatment.The combined PTT/PDT synergic therapy led to an outstanding therapeutic efficiency for cancer cell treatment.2.The rattle-type Au@Cu2-xS hollow mesoporous nanoparitcles with advanced PCE were designed as cellular vehicles and chemo-photothermal synergistic therapy platform.The localized surface plasma resonance(LSPR)coupling between the Au core and Cu2-xS shell were investigated experimentally and theoretically to generate a PCE high to 35.2%and enhanced by 11.3%than that of Cu2-xS.By conjugating miRNA gene probe on the surface,it could realize the intracellular oncogenic miRNA detection.After loading of anticancer drug doxorubicin(DOX)into the cavity of the Au@Cu2-xS,the antitumor therapy efficacy was greatly enhanced due to the NIR photoactivation chemo-and photothermal synergistic therapy.The rattle-type metal-semiconductor hollow mesoporous nanostructure with efficient LSPR coupling and high cargo loading capability would be beneficial to future design of LSPR-based photothermal agents for a broad range of biomedical application.3.An intelligent MnO2/Cu2-xS-siRNA nanoagent simultaneously overcoming inherent limitations of PDT and PTT with remarkable PTT/PDT therapeutic efficiency enabling multimode accurate tumor imaging diagnostic was designed.We first develop a general method to decorate Cu2-xS on the surface of MnO2 nanosheet(MnO2/Cu2-xS),then,it was loaded with heat shock protein(HSP)70 siRNA to obtain MnO2/Cu2-xS-siRNA.The intracellular miRNA imaging could be realized by loading miRNA detection probes.In the tumor acidic microenvironment,the MnO2 was reduced to Mn2+ ion,and trigger the decomposition of H2O2 into O2 to relieve tumor hypoxia.The reduced Mn2+ ions significantly enhanced magnetic resonance imaging(MRI)contrast and the Cu2-xS acted as a powerful photoacoustic(PA)and photothermal(PT)imaging agent,leading to tri-modal accurate tumor-specific imaging and detection.Under a single NIR laser irradiation,the nanosystem exhibited superiority of PTT/PDT efficiency owing to siRNA-mediated blocked heat-shock response and MnO2-related relieved tumor hypoxia.This work highlighted the great promise of modulating tumor cellular defense mechanism and microenvironment with intelligent multifunctional nanoagents to achieve a comprehensive fighting cancer effect.4.A strategy of the low-temperature nucleus-targeted PTT in the NIR-?region achieving effective tumor killing was introduced by combing of the vanadium carbide quantum dots(V2C QDs)PTA and engineered exosomes(Ex)vector.The small fluorescent V2C QDs with good photothermal effect in the NIR-II region were modified with TAT peptides and packaged into Ex with RGD modification(V2C-TAT@Ex-RGD).Compare to the photothermal agents active in the NIR-I biowindow,the V2C-TAT@Ex-RGD displayed deeper penetration depth.The resulting nanoparticles(NPs)exhibited good biocompatibility,long circulation time and endosomal escape ability,and it could target the cell and enter into nucleus to realize low-temperature PTT with advanced tumor destruction efficiency and less side effects.The fluorescent imaging,photoacoustic imaging(PAI)and magnetic resonance imaging(MRI)capability of the NPs was also revealed.The mutimodel imaging guided low-temperature nucleus-targeted PTT in NIR-? region provides more possibilities toward successful clinical application of PTT.