Construction Of Responsive Iron-Based Nanoparticle And Exploration In Tumor Diagnosis And Therapy

Iron-based nanomaterials have been widely used in the fields of catalysis,biotechnology,biomedicine,magnetic resonance imaging,biosensors and tumor therapy due to their special physicochemical properties.Especially,iron-based nanomaterials have great potential for tumor diagnosis,magnetic hyperthermia,photodynamic therapy and iron death therapy.However,most iron-based nanomaterials are always"on"when imaging and treating tumors,which could affect normal tissues and reduce the specificity of tumor imaging and therapy.For the above-mentioned problems,herein we have constructed responsive iron-based nanoparticles to improve the specificity for tumor imaging and therapy,thus enhancing the therapeutic effect and reducing the toxic side effects.The main research elements are as follows:（1）We have constructed H₂O₂-responsive iron-based nanoparticle for the combined treatment of iron death and chemodynamic.Firstly,we prepared H₂O₂-responsive polymer（RP）and assembled it with Fe₃O₄ nanoparticles and chemotherapeutic drug doxycycline（Dox）to construct H₂O₂-responsive therapeutic nanoplatform（Dox-Fe@RP）.In the presence of H₂O₂,the surface polymer of Dox-Fe@RP undergoes a hydrophile transition to induce the release of Fe₃O₄ and Dox,leading to changes in structure,fluorescence intensity and saturation magnetization rate.The released Fe₃O₄nanoparticles catalyze·OH production from H₂O₂ and deplete GSH,causing lipid peroxidation and iron death in cancer cells.The released Dox can up-regulate the intracellular H₂O₂ level in cancer cells,further enhancing the above catalytic effect and realizing the combined treatment of chemotherapy and iron death.Moreover,the MRI signal of Dox-Fe@RP changes in the presence of H₂O₂,allowing the activation process to be monitored by MRI imaging.（2）We constructed alkali-responsive magnetic nanoparticle for specific imaging.Based on the coordination of metal ions with-CN,we successfully prepared Fe/Mn/Gd-CN-coordinated magnetic nanoparticles（MICN）with excellent near-infrared（NIR）absorption and relaxation effects.MICN is structurally stable with high photoacoustic,photothermal and MRI signals when MICN is present in acidic solutions.However,MICN structure is destroyed by hydroxide when MICN is present in alkaline solution,which reduces the NIR absorption and relaxation effect,thus significantly reducing the photoacoustic,photothermal and MRI signals.Due to the properties of tumor microacids,MICN-PEG exhibits good photoacoustic imaging,photothermal imaging and MRI imaging effects when MICN-PEG is concentrated in tumors;at the other hand,MICN-PEG exhibits significantly lower photoacoustic imaging,photothermal imaging and MRI imaging signals in normal tissues,thus significantly improving the specificity of tumor imaging.