Photothermal/chemodynamic Synergistic Therapy Of Tumor With Au NRs@MnO₂-PEG

Nowadays the morbidity and mortality of tumors remain high and the current clinical treatment methods are not sufficient to solve the worldwide challenge of cancer therapy.Although some new tumor treatment methods have been proposed for some time,it is difficult to realize clinical application due to the complexity of the tumor and the limitations of the treatment methods themselves.Therefore,proposal of new tumor therapy strategy and improvement of the current tumor therapy methods are highly important.Chemodynamic therapy is a recently proposed concept of cancer treatment.Due to the close combination of the treatment principle and the tumor microenvironment(TME),it has the advantages of endogenous activation,high selectivity,and clear therapeutic logic over other tumor treatments.However,the slow catalytic reaction rates in the tumor region restrict clinical application of the chemodynamic therapy.In fact,most reported tumor treatment effects of the chemodynamic therapy are inhibitory effects.To promote the chemodynamic therapy in clinical application,in this dissertation,a novel composite nanoparticle is synthesized and used for photothermal/chemodynamic synergistic therapy of tumor.Firstly,gold nanorods(Au NRs)are synthesized by a seed method.Next,manganese dioxide(MnO2)is coated on the Au NRs by a redox method.Finally,core-shell structured Au NRs@MnO2-PEG NPs are obtained after a polyethylene glycol(PEG)modification process through a layer-by-layer self-assembly method.On the one hand,MnO2 can consume glutathione overexpressed in tumor regions thus reduce its consumption of hydroxyl radicals.Meanwhile,the release of Mn2+during the process can catalyze the overexpression of hydrogen peroxide in the tumor area to form hydroxyl radical for chemodynamic therapy.At the same time,Mn2+can be used for tumor imaging and monitoring of chemodynamic therapy processes.As a result,the Au NRs@MnO2-PEG NPs can use for high-performance cancer chemodynamic therapy and tumor imaging.Furthermore,Au NRs can produce hyperthermia-induced apoptosis under an 808 nm laser irradiation and provide thermal stimulation for chemodynamic therapy to enhance the therapeutic effect.More promisingly,the PEG modification and the suitable nanoscale sizes contribute to the enrichment of the Au NRs@MnO2-PEG NPs in the tumor regions.Finally,the Au NRs@MnO2-PEG nanoparticles prepared by us can achieve about 90%killing effect in in vitro cell experiments,and the tumor position can be accurately located in magnetic resonance imaging experiments.The measured tumor volume of the mice after the synergistic treatment is very close to zero and no recurrence were identified,indicating that the Au NRs@MnO2-PEG NPs have excellent in vivo photothermal/chemodynamic synergistic therapy performance.