Aubrey Jacob D, Gibson James, Leman John T, Yeh Benjamin M, Bonitatibus Peter J
Department of Chemistry and Chemical Biology, Renssalaer Polytechnic Institute, Troy, NY 12180-3522, USA.
Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA 94143-0628, USA.
Acad Nano. 2025;2(2). doi: 10.20935/acadnano7737. Epub 2025 May 29.
Tantalum oxide nanoparticles (TaO NPs) are promising as high--contrast agents for computed tomography (CT) due to their profound imaging benefits relative to those of clinical iodinated contrast media (ICM) at the X-ray tube voltages ≥100 kVp required for most patients. Furthermore, TaO NPs have prevailed through extensive non-GLP and GLP (good laboratory practice) preclinical development, including in vivo/vitro safety testing and imaging efficacy studies. This is due in part to innovative structural engineering of the NPs' core size and coating, which has been shown to provide favorable pharmacokinetics and promote rapid renal clearance, with negligible organ retention. In this study, a carboxybetaine zwitterionic siloxane polymer (CZ) coating for a lead candidate TaO NP is thoroughly characterized using multinuclear/multidimensional nuclear magnetic resonance (NMR) spectroscopic techniques. H and H/C heteronuclear multiple bond correlation NMR spectroscopies are used to confirm the CZ coating's structure, and in combination with Si NMR, the architecture of the siloxane coating bound to the TaO NPs' surface is described. Of particular significance, Si NMR spectra were used to identify the T-region bonding modes of the CZ coating and show the superiority of diafiltration over dialysis for purification of the TaO NPs. Through a spectral comparison, a cyclic siloxane impurity in the TaO NP product purified through dialysis was found to be absent in the product purified through diafiltration. Finally, the H Carr-Purcell-Meiboom-Gill (CPMG) NMR pulse sequence was used in a novel manner to probe the distance-dependent interactions between the H spins of the CZ coating and the TaO NPs' surface.
氧化钽纳米颗粒（TaO NPs）有望成为计算机断层扫描（CT）的高对比度造影剂，因为在大多数患者所需的X射线管电压≥100 kVp时，相对于临床碘化造影剂（ICM），它们具有显著的成像优势。此外，TaO NPs已通过广泛的非GLP和GLP（良好实验室规范）临床前开发，包括体内/体外安全性测试和成像功效研究。这部分归功于纳米颗粒核心尺寸和涂层的创新结构工程，已证明其具有良好的药代动力学，并能促进快速肾清除，器官滞留可忽略不计。在本研究中，使用多核/多维核磁共振（NMR）光谱技术对一种主要候选TaO NP的羧基甜菜碱两性离子硅氧烷聚合物（CZ）涂层进行了全面表征。1H和1H/13C异核多键相关NMR光谱用于确认CZ涂层的结构，并结合29Si NMR描述了与TaO NPs表面结合的硅氧烷涂层的结构。特别重要的是，29Si NMR光谱用于识别CZ涂层的T区域键合模式，并显示了渗滤相对于透析在TaO NPs纯化方面的优越性。通过光谱比较，发现通过透析纯化的TaO NP产品中存在的环状硅氧烷杂质在通过渗滤纯化的产品中不存在。最后，H Carr-Purcell-Meiboom-Gill（CPMG）NMR脉冲序列以一种新颖的方式用于探测CZ涂层的H自旋与TaO NPs表面之间的距离依赖性相互作用。
