The Controllable Synthesis And Performance Research Of Paramagnetic NaGdF₄-based Nanoscale MRI Contrast Agents

The magnetic resonance imaging?MRI?is becoming a kind of indispensable important clinical medicaldiagnostic tools due to the rapid development of medical diagnostic technology.Nanotechnology also brought new important opportunities to the development of magnetic resonance imaging?MRI?contrast agents.Low-dimensional NaGdF₄-based nanomaterials are expected to become a new generation of magnetic resonance imaging?MRI?contrast agents,which are high efficiency and low toxicity,to be applied to clinical benefit mankind in the future because of strong physical and chemical stability and high magnetic resonance imaging?MRI?relaxivity.In this dissertation,uniform sub-10 nm NaGdF₄ nanocrystal was synthesized using a facile high temperature organic solution method according to the LaMer nucleation and growth model.The NaGdF₄ nanocrystal modified using PEG-PAA polymer exhibited a high r1 of 7.0 mM^-1s^-1,twice of that of commercially used gadopentetate dimeglumine?Gd-DTPA?.Moreover,lyophilized powder of this modified NaGdF₄ nanocrystal has been successfully prepared,which can be re-dispersed into aqueous injection without aggregation or reduction of MR performance.No cyto-toxicity and haemolysis was induced by the NaGd F₄ nanocrystal,and no leakage of gadolinium ion was observed.Compared with Gd-DTPA injection,MR angiography on rabbit using NaGdF₄ nanocrystals at a low dose shows distinct vascular details and long circulation time.All kinds of safety analysis in vitro and in vivo prove that our ppNaGdF₄ is expected to become a new generation of magnetic resonance imaging?MRI?contrast agents,which are high efficiency and low toxicity,to be applied in clinical blood pool imaging.We demonstrated a facile sequential growth method to synthesize uniform sub-10 nm ?-NaGd F₄:Yb,Er@CaF₂ core-shell nanocrystals according to the LaMer nucleation and growth model.Because of the existence of outer CaF₂ layer,the as-prepared ?-NaGdF₄:Yb,Er@CaF₂ core-shell nanoparticles can effectively reduce thepotentialleakage of Gd³⁺ in the core layer of NaGd F₄:Yb,Er nanocrystals.Compared to the NaGdF₄:Yb,Er core nanocrystals,its upconversion fluorescence also improved 2-3 times,and after modified with the polyacrylic acid?PAA?,the ?-NaGdF₄:Yb,Er@CaF₂-PAA nanoparticles show a r1 of 6.04 mM^-1s^-1 under 3.0 T magnetic field,higher than that of commercial contrast Gd-DTPA with r1 of 4.24 mM^-1s^-1.Its high chemical stability and strong upconversion fluorescence performance and good T₁ magnetic resonance imaging performance render it to become a kind of potential clinical dual-mode molecular probes for upconversion fluorescence imaging and magnetic resonance imaging?MRI?.In a word,we demonstrated simple method to synthesize two low dimensional NaGdF₄ nanoscale magnetic resonance imaging?MRI?contrast agents with good T₁ magnetic resonance imaging performance,namely ppNaGdF₄ nanocrystals lyophilized injection and ?-NaGdF₄: Yb,Er@CaF₂-PAA nanocrystals.A lot of experiments proved that these safe and effective nanoscale magnetic resonance imaging?MRI?contrast agents will be used in clinical medicine and benefit mankind in the furture.