Controlled Synthesis Of Zn_xMn_1-xS@PDA Nanostructure And Its Application In Tumor Theranostic

Tumor microenvironment(TME)was characterized by weak acidity,overexpression of hydrogen peroxide(H₂O₂)and glutathione(GSH),low catalase activity and hypoxia.As an emerging anticancer strategies for TME,chemodynamic therapy(CDT)had been widely researched with its advantages of high specificity and low invasive treatment.In the process of CDT,tumor endogenous H₂O₂ was decomposed into hydroxyl radical(·OH)by Fenton reaction or Fenton like reaction by metal catalysts(such as Fe,Mn,Cu,Co,etc.).·OH was the most harmful reactive oxygen species(ROS)could induce cancer cell death through oxidative damage of lipids,proteins and DNA with high electrochemical oxidation potential(E(·OH/H₂O)=+2.80 V).However,due to the limited concentration of H₂O₂(50-100?m)in tumor cells,the production of·OH was not enough to eliminate the tumor completely.The ROS could be cleared by the reducing agent GSH in the TME,which limited the therapeutic effect of CDT.To solve the above problems,this thesis designed a Zn_xMn_1-xS@PDA tumor treatment nanosystem to enhance CDT through the consumption of GSH and photothermal effect,and realized the synergistic treatment of tumor by CDT and photothermal therapy(PTT).The main work and conclusions are as follows:The high activity Zn_xMn_1-xS hollow nanospheres with different molar ratios of Zn and Mn were prepared by solvothermal method.The morphology of Zn_xMn_1-xS hollow nanospheres with different molar ratios of Zn and Mn were characterized by transmission electron microscopy(TEM).The sample with 1:1 molar ratio of Zn and Mn had ideal hollow nanostructures,which could be used for subsequent experiments.The hollow nanospheres(Zn_xMn_1-xS@PDA)were obtained by modifying polydopamine(PDA)shells of different thickness on the surface of the hollow spheres by dopamine oxidation self-polymerization.The PDA shells can regulate the release of manganese ions in vivo and in vitro.Zn_xMn_1-xS@PDA with different PDA shell thickness were co-cultured with human umbilical vein endothelial cells(HUVEC)and mouse breast cancer cells(4T1),it was found that Zn_xMn_1-xS@PDA with the mass of 1:1 and the shell thickness of PDA about 5 nm had the best biocompatibility and anti-tumor effect.The chemodynamic and photothermal properties of the Zn_xMn_1-xS@PDA hollow nanospheres were studied.The results showed that the hollow nanospheres exhibit strong near-infrared light absorption and high photothermal conversion efficiency(32.79%).In the presence of trace H₂O₂,H₂O₂ could be converted into highly toxic·OH through Fenton-like reaction.Meanwhile,photothermal effect could promote the electron transfer of Fenton-like reaction,promoted the production of·OH,and enhanced the therapeutic effect of CDT.In addition,the transition metal ion Mn⁴⁺with high oxidation state in the nanoparticles had reversible redox properties,which could remove GSH and enhanced the therapeutic effect of tumor.The study of mouse breast cancer model showed that the nanoparticles could completely eliminate the tumor through CDT and PTT synergistic treatment.The results of blood routine tests,blood biochemical indexes and H&E staining images of important organs in mice showed that Zn_xMn_1-xS@PDA had good biological safety.