【作者】 杨建峰；

【导师】 张兴华；

【作者基本信息】 河北工业大学 ， 材料物理与化学， 2021， 硕士

【摘要】 磁共振成像（MRI）是一种重要的生物成像手段,但目前商用磁共振造影剂Gd-DTPA等存在成像性能差、对肾功能障碍患者具有潜在肾纤维化风险的问题,限制了其生物成像应用。钆基纳米颗粒具有较好的成像效果和稳定性,在磁共振成像方面具有广阔的应用前景。但是,钆基纳米颗粒的弛豫增强机理尚缺乏系统和深入的研究。本文以钆基纳米颗粒作为研究对象,制备了不同尺寸、表面配体修饰的钆基纳米颗粒,并探究了表面基团对钆基纳米颗粒的弛豫增强机理;结合理论分析,探究了钆基纳米颗粒的弛豫增强机制及设计策略,并进一步结合金纳米棒（Au NRs）应用于多模态成像领域。内容如下:首先,利用热分解法制备了尺寸相近的GdF₃、Na Gd F₄、Gd₂O₃纳米颗粒,测试发现,Gd₂O₃纳米颗粒的弛豫速率较高。此外,利用共沉淀法合成了不同表面配体修饰的Gd₂O₃纳米颗粒,其颗粒尺寸随着表面配体与钆源比例的增加而减小;通过对比发现聚丙烯酸（PAA）修饰的Gd₂O₃纳米颗粒的弛豫性能最佳,其纵向弛豫速率（r₁）值为53.34 m M^-1 s^-1,达到商用Gd-DTPA的14倍,这主要源于PAA中羧基与水分子之间存在较强的氢键结合力。其次,利用SBM理论,结合内球层与外球层弛豫机制,定量研究了动力学参数对纳米颗粒的弛豫作用影响。模拟结果表明,内球层在纳米颗粒的弛豫作用中起主要作用;内球层弛豫中,翻转运动时间（τ_R）和停留时间（τ_M）的影响较大,内球层弛豫速率(r₁^IS)随τ_R的增加而增大,随τ_M的增加先增大后减小,而纵向电子弛豫时间(T_1e)的影响较小且主要集中在低频区;外球层弛豫中,外球层弛豫速率(r₁^OS)随扩散时间（τ_d）的增加而减小,随T_1e的增加而增大且主要集中在低频区;此外,水合粒径对r₁的影响较大,高T₁ MRI性能的钆基纳米颗粒的设计策略在于合理调控水合粒径尺寸,最佳水合粒子半径范围为0.8-2.5nm。最后,将Gd₂O₃纳米颗粒与AuNRs复合制备了Gd₂O₃/Au NRs复合纳米材料,Gd₂O₃负载量对复合纳米材料的弛豫作用影响较大,负载量的增加使其具有更大的水化数（q）,从而实现更高的弛豫增强效果。Gd₂O₃/Au@MSNs的最大r₁值为64.53 m M^-1 s^-1,达到商用造影剂的17倍,r₂/r₁为1.04,CT成像效果也优于商用造影剂,具有较好的成像敏感性和生物相容性,具有多模态成像的应用潜力。更多还原

【Abstract】 Magnetic resonance imaging（MRI）is an important biological imaging tool.However,the current commercial MRI contrast agents such as Gd-DTPA have the problems of poor imaging performance and potential nephrotoxicity risk to patients with poor renal function,which limits the application in biological imaging.Gd based nanoparticles have great potential applications in magnetic resonance imaging due to their good imaging effect and high stability.However,the relaxivity enhancement mechanism of Gd based nanoparticles is still lack of systematic and in-depth research.In this thesis,Gd based nanoparticles with different sizes and surface ligands were prepared,and the relaxivity enhancement mechanism of surface groups on Gd based nanoparticles was explored.Combined with theoretical analysis,the relaxivity enhancement mechanism and design strategy of Gd based nanoparticles were explored.By bonding with the Au nanorods（Au NRs）,Gd based nanoparticles were further applied in the field of multimodal imaging.The contents are as follows:Firstly,GdF₃,NaGdF₄ and Gd₂O₃ nanoparticles with similar size were prepared with a thermal decomposition method.It was found that Gd₂O₃ nanoparticles had higher relaxivity.In addition,Gd₂O₃ nanoparticles coated with different surface ligands were synthesized by a coprecipitation method,and the particle size decreased with the increase of the ratio of surface ligands to Gd source.By comparison,it was found that Gd₂O₃ nanoparticles modified by polyacrylic acid（PAA）had the best relaxation property,with longitudinal relaxivity（r₁）value of 53.34 m M^-1 s^-1,which was 14 times higher than that of Gd-DTPA.This was mainly induced by the strong hydrogen bonding between water molecule and carboxyl group in PAA.Secondly,the effect of kinetic parameters on the relaxation of nanoparticles was quantitatively studied by the inner-sphere and outer-sphere mechanism with SBM theory.The simulation results show that the inner-sphere plays a major role in the relaxation of nanoparticles.For the inner-sphere relaxation,the motional time（τ_R）and residence time（τ_M）play an impotant role,the inner-sphere relaxivity(r₁^IS)increases with the increase ofτ_R,and r₁^IS first increases and then decreases with the increase ofτ_M,while the effect of longitudinal electron relaxation time(T_1e)is little and mainly concentrated in the low frequency.For the outer-sphere relaxation,the out-sphere relaxivity(r₁^OS)decreases with the increase of diffusion time（τ_d）,and r₁^OS increases with the increase of T_1e,which is also concentrated in the low frequency.Moreover,the hydrated particle size has a greater influence on r₁.The design strategy of Gd based nanoparticles with high T₁ MRI performance is to reasonably control the hydration particle size,and the optimal hydration particle radius range is 0.8-2.5 nm.Finally,Gd₂O₃/AuNRs composite nanomaterials were prepared by combining Gd₂O₃nanoparticles with Au NRs.The loading amount of Gd₂O₃ has a great influence on the relaxivity of the composite nanomaterials.The increase of the loading amount can enhance the hydration number（q）of the composite nanomaterials,thus improving the ralaxivity.The maximum r₁ value of Gd₂O₃/Au@MSNs is up to 64.53 m M^-1 s^-1,which is 17 times than that commercial contrast agent,and r₂/r₁ is 1.04.The CT imaging performance of Gd₂O₃/Au@MSNs is better than that of commercial contrast agent.Moreover,Gd₂O₃/Au@MSNs has a good imaging sensitivity and biocompatibility,which has great potential application in multimodal imaging.更多还原