Based On Fe@Fe₃O₄ Nanoparticles For T₁-T₂ Bimodal MRI Contrast Agent And The Application Of Magnetic Hyperthermia Reagents

Magnetic resonance imaging?MRI?is widely used in clinical medical diagnosis due to its noninvasive character,high soft tissue contrast,large penetration depth and outstanding spatial resolution.In addition,in order to further to improve the contrast of MRI,it is necessary to use an MRI contrast agent.MRI contrast agents can be further divided into positive?T₁?and darkened negative?T₂?contrast agents that brighten the lesion.Since a single MRI angiography mode can cause a lot of signal interference,the development of T₁-T₂ dual-mode contrast agent is of great significance.This kind of contrast agent can realize dual-mode imaging on the same instrument,which can greatly improve the diagnosis.In addition,based on the magnetocaloric conversion properties of magnetic materials,the development of an integrated reagent for both MRI diagnosis and magnetocaloric therapy can not only achieve the early diagnosis of tumors,but also achieve in situ treatment of the lesions found,alleviate the pain of patients,which has important clinical significance.Based on this,the following two work were carried out with Fe@Fe₃O₄ nanoparticles with good biocompatibility and simple preparation in this paper.First,based on T₂-weighted imaging performance of Fe@Fe₃O₄ and commercial T₁-weighted imaging contrast agent?DOTA-Gd?,Gd-labeled Fe@Fe₃O₄ nanoparticles were designed and developed for T₁-T₂ dual-mode MRI contrast agents.The oleic acid/oleylamine coated Fe@Fe₃O₄ nanomaterials were prepared by high temperature pyrolysis method,and then the amino functionalized Fe@Fe₃O₄ nanomaterials were prepared by surface modification with alendronate sodium?ALA?.Finally,a T₁-T₂ dual-mode MRI contrast agent was prepared by coupling DOTA?Gd?to the surface of Fe@Fe₃O₄ by bio-coupling reaction.In addition,the relaxation rate of Fe@Fe₃O₄@RAW is twice that of Fe@Fe₃O₄,and the contrast of T₂-weighted imaging is greatly improved.The contrast agent exhibits excellent T₁-T₂ bimodal imaging performance,after 30 minutes of intratumoral injection,the T₁ imaging intensity of the tumor site increased by 70%and the T₂ imaging contrast decreased by 20%.Secondly,based on the phagocytosis of macrophages,Fe@Fe₃O₄ magnetotherapy reagent loaded by macrophages was prepared,and its application in cancer treatment was explored.Fe₃O₄ nanoparticles was incubated with RAW246.7 cells to obtain Fe@Fe₃O₄@RAW magnetic hyperthermia reagent.Compared with Fe@Fe₃O₄,the magnetocaloric performance of Fe@Fe₃O₄@RAW has been improved twice,and the magnetocaloric stability is still very high after six cycles.More importantly,Fe@Fe₃O₄@RAW can effectively treat 4T1 cells under the action of an external magnetic field.Through the work of this paper,it not only provides a dual-mode contrast agent for the diagnosis of cancer,but also provides a new therapeutic reagent for the treatment of cancer,which further promotes the development of Fe@Fe₃O₄ nanomaterials and provides theoretical support for its clinical transformation.