Construction Of Mn²⁺-doped Core/Shell Magnetic Upconversion Nanomaterials And Its Application In Biological Imaging

In recent years,the rare-earth ions doped upconversion nanoparticles?UCNPs?have attracted the attention of researchers in biological imaging field because of its unique properties,which could absorb two or more than two low energy photons to radiate a high energy photon.As we all know,the Yb³⁺/Er³⁺(or Yb³⁺/Tm³⁺)co-doped has been reported as the efficient NIR?980 nm?-to-visible light?red and green?and near infrared light UCNPs,which falls within the“optical window”that will have a certain prospect for bioimaging.Nevertheless,many UCNPs could not be applied into biomedical field directly,not only because of its lower fluorescence intensity but also mixed multi-wavelength fluorescence.However a new and effective method to solve these problems by doping Mn²⁺,due to Mn²⁺could not only improve the efficiency of UCNPs,but also achieve single red luminescent.In addition,a large number of hydrophobic groups are ususlly coated on the surface of UCNPs,which seriously restricts its application in field of biomedicine.So it is also necessarily to synthesis water-soluble UCNPs.On the other hand,gadolinium?Gd?or manganese?Mn?based nanodevices have been widely studied for T₁-weighted MR imaging;superparamagnetic iron oxide?Fe₃O₄?nanoparticles?NPs?are used as ideal probes for T₂-weighted MR imaging in field of magnetic resonance imaging?MRI?.Therefore,we hope to combine UCNPs with nanoparticles that coexistence of Mn and Fe₃O₄,which may be not only applied into T₁/T₂-weighted multi-mode MRI,but also for biological imaging.In addition,photodynamic therapy?PDT?has received great interest for researchers because of its efficient treatment.Chlorin e6?Ce6?could effectively generate reactive oxygen species?ROS?after red light?660 nm?irradiation as a photosensitizer,which can be used to kill cancer cells.However,Ce6 could not be used in the biological field due to poor water solubility.Therefore,we constructed a water-soluble magnetic fluorescent upconversion nanomaterials coated by Ce6 for MRI,bioimaging and PDT.Based on these,the following aspects was included in this work:?1?Preparation of water-soluble Mn²⁺-doped NaYF₄:Yb³⁺/Er³⁺NPs.In this paper,the oleic acid?OA?coated Mn²⁺-doped NaYF₄:Yb³⁺/Er³⁺NPs were synthesized by hydrothermal method using the rare-earth nitrate as the raw material firstly.Then OA coated Mn²⁺-doped NaYF₄:Yb³⁺/Er³⁺NPs are transferred into water through the ligand-exchange method?or polymer coating method?,using triton-phosphateas(or amphiphilic polymer(C₁₈PMH-mPEG))as hydrophilic ligands.Subsequently,the samples are characterized with transmission electron microscopy?TEM?,dynamic light scattering?DLS?,X-ray diffraction?XRD?,fluorescence spectrophotometer,fourier transform infrared spectroscopy?FTIR?and thermogravimetric analyzer?TGA?.?2?Synthesis of Fe₃O₄@Mn²⁺-doped NaYF₄:Yb/Tm magnetic fluorescent NPs.OA coated Fe₃O₄ NPs were prepared by coprecipitation method,and then OA-Fe₃O₄ used as seeds and core coated by Mn²⁺-doped NaYF₄:Yb/Tm upconversion fluorescent shell through the hydrothermal method.OA coated Fe₃O₄@Mn²⁺-doped NaYF₄:Yb/Tm magnetic fluorescent NPs were acquired at last.The crystal phase and fluorescence intensity of these NPs were tuned by doping Mn²⁺.Then,the hydrophobic Fe₃O₄@Mn²⁺-doped NaYF₄:Yb/Tm NPs could be transferred into water after coating them with a layer of amphiphilic poly?maleic anhydride-alt-1-octadecene?(C₁₈PMH)modified with amine functionalized methylether poly?ethylene glycol?(C₁₈PMH-mPEG).Finally,the obtained hydrophilic NPs were used as contrast agents for NIR-to-NIR luminescent imaging and T₁/T₂-weighted MRI.?3?Influence of Mn²⁺doping on the formation of core-shell structured Fe₃O₄@NaYF₄?Yb/Er?composite NPs.The role of Mn²⁺doping on the synthesis of core-shell structured magnetic-upconversion nanoparticles?MUCNPs?is investigated through seed growth method under the condition of hydrothermal.The morphology and crystal phase of the prepared MUCNPs were then characterized by transmission electron microscopy?TEM?and X-ray diffractometer?XRD?.Additional experiments were conducted in which only NaF was introduced into this system in the presence of oleic acid coated Fe₃O₄?OA-Fe₃O₄?NPs,precipitating the obtained product.X-ray photoelectron spectra?XPS?were then used to examine the composition of the precipitated product.?4?Synthesis of Fe₃O₄@Mn²⁺-doped NaYF₄@Mn²⁺-doped NaYF₄:Yb³⁺/Er³⁺core/shell/shell magnetic fluorescent NPs and their applications in bioimaging and near-infrared activated PDT.The core/shell/shell magnetic fluorescent nanoparticles?C/S/S-MUCNPs?with Fe₃O₄ as the core,an inert layer of Mn²⁺-doped NaYF₄ and an outer shell consisted of Mn²⁺-doped NaYF₄:Yb³⁺/Er³⁺were prepared.To further develop these C/S/S-MUCNPs applications in biological field,C₁₈PMH-mPEG was used as a capping ligand to modify the C/S/S-MUCNPs.Then the UCL imaging,T₁-weighted MRI ascribed to the Mn²⁺ions,and T₂-weighted MRI ascribed to the Fe₃O₄ core of C/S/S-MUCNPs were evaluated.Finally,chlorine e6?Ce6?was loaded on the mPEG-C/S/S-MUCNPs,and the PDT performance of these NPs was explored.