Antifouling Manganese Oxide Nanoparticles: Synthesis, Characterization, And Applications For Enhanced MR Imaging Of Tumors

With the development of nanotechnology and nanomedicine,manganese oxide?Mn₃O₄?nanoparticles?NPs?as positive contrast agents have attracted wide interest in the field of magnetic resonance?MR?imaging.In order to improve the sensitivity of disease detection,multifunctional Mn₃O₄ NPs,which can be highly enriched in lesions to achieve excellent MR imaging ability,have been developed.In our previous work,polyethylenimine?PEI?-coated Mn₃O₄ NPs were successfully synthesized,functionalized via amino groups of PEI,and used as targeted MR imaging contrast agent of tumor.In another work,by using sodium citrate?Na₃Cit?as stabilizer,we fabricated super-small iron oxide?Fe3O4?NPs which can be multifunctionalized via carboxyl groups on NPs for targeted T₁-weighted MR imaging of tumor.However,due to the relatively low T₁ relaxation rate?0.566 m M-1s-1?,large dose of PEI-coated Mn₃O₄ NPs is necessary for MR imaging,resulting in a great burden and presumably damage on the liver and kidney.Furthermore,under the same crystallization conditions,the size of magnetic particles is closely related to its relaxation rate.Na3 Cit,as both reducing agent and stabilizer,played a key role in the synthesis of ultrasmall Fe3O4 NPs?2.8 nm?.Inspired by our recent work,in this thesis we attempted to synthesize and functionalize Mn₃O₄ NPs with high relaxation rate in order to improve the diagnostic accuracy of MR imaging.Na₃Cit-stabilized Mn₃O₄ NPs with high relaxation rate were first synthesized using solvothermal method,and the formed Mn₃O₄ NPs were then successively conjugated with polyethylene glycol?PEG?and L-cysteine on the surface to obtain multifunctional,especially antifouling Mn₃O₄ NPs for T₁-weighted MR imaging of C6 glioma?a rat C6 glioma cell line?subcutaneous tumor model.The results indicate that the formed Mn₃O₄ NPs with a diameter of about 2.7 nm display good colloidal stability and biocompatibility,and the T₁ relaxation rate?r1?is up to 3.66 m M-1s-1.The L-cysteine modified Mn₃O₄ NPs have a longer blood circulation time than Mn₃O₄ NPs without L-cysteine modification.In vitro and in vivo MR imaging results suggest that L-cysteine modified Mn₃O₄ NPs display much better MR imaging ability for both C6 cells and C6 xenografted tumor model.What's more,in vivo biodistribution reveals that the NPs also can be metabolized in the body,leaving no visible damage to normal organs.In summary,we have prepared Mn₃O₄ NPs with antifouling properties and high T₁ relaxation rate,which can enhance diagnostic accuracy of MR imaging.The ideas and findings from this thesis provide a new thought for developing MR imaging contrast agents with high diagnostic accuracy and sensitivity or other biological antifouling platforms.