Construction Of Manganese-doped Ultrasmall Inorganic Nanoprobes And Their Application In Visualized Theranostics Of Tumor

Inorganic nanomaterials with ultrasmall size have the characteristics of renal clearance,which is very significant for the clinical application of inorganic nanoprobes.Manganese ion(Mn²⁺)has the performances of magnetic resonance imaging(MRI)and tumor-microenvironment-responsive chemodynamic therapy(CDT).Therefore,it was an important strategy of constructing Mn²⁺-doped inorganic nanoprobes,achieving safe and metabolizable visualized theranostics.In this dissertation,based on ultrasmall carbon nanodots(CDs)and gold nanoclusters(Au NCs),two kinds of Mn²⁺-doped inorganic nanoprobes with ultrasmall size were constructed to realize dual-modal imaging and visualized theranostics.The main findings were summarized as follows:(1)Mn²⁺-doped CDs(Mn-CDs)nanoprobs with ultrasmall size was prepared to realize fluorescence(FL)imaging and MRI of tumor.The results showed Mn-CDs nanoprobe was synthesized by one-step solvothermal method,in which Mn-CDs had uniform size(5 nm)and good dispersibility.By Mn²⁺doping,Mn-CDs nanoprobe occupied enhanced FL emission and emission wavelength can red-shift from 542 nm to 578 nm,which was attributed to the increasing nitrogen content.Due to doping of Mn²⁺,the Mn-CDs nanoprobe showed excellent T₁-weighted MRI performance with a longitudinal relaxation rate of 12.69 m M^-1·s^-1.In addition,Mn-CDs nanoprobe had good in vivo/in vitro biocompatibility and FL/MRI performance.(2)Mn²⁺-doped Au NCs(Mn-Au NCs)nanoprobe with ultrasmall size was prepared to realize MRI and synergistic photodynamic therapy(PDT)/CDT of tumor cells.The results showed that Mn-Au NCs nanoprobe had the size of about 3 nm,excellent FL imaging and T₁-weighted MRI performance,in which the optimal FL emission wavelength was about 690nm and the longitudinal relaxation efficiency was as high as 31.71 m M^-1·s^-1.Mn-Au NCs nanoprobe showed hydrogen peroxide(H₂O₂)-responsive hydroxyl radicals(·OH)and oxygen(O₂)generation.Under the combination of PDT/CDT,the viability of 4T1 cells can be reduced to 8%.