Bruckman Michael A, Hern Stephen, Jiang Kai, Flask Chris A, Yu Xin, Steinmetz Nicole F
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA.
J Mater Chem B. 2013 Mar 14;1(10):1482-1490. doi: 10.1039/C3TB00461A.
To compensate for the low sensitivity of magnetic resonance imaging (MRI), nanoparticles have been developed to deliver high payloads of contrast agents to sites of disease. Here, we report the development of supramolecular MRI contrast agents using the plant viral nanoparticle tobacco mosaic virus (TMV). Rod-shaped TMV nanoparticles measuring 300×18 nm were loaded with up to 3,500 or 2,000 chelated paramagnetic gadolinium (III) ions selectively at the interior (iGd-TMV) or exterior (eGd-TMV) surface, respectively. Spatial control is achieved through targeting either tyrosine or carboxylic acid side chains on the solvent exposed exterior or interior TMV surface. The ionic T relaxivity per Gd ion (at 60 MHz) increases from 4.9 mMs for free Gd(DOTA) to 18.4 mMs for eGd-TMV and 10.7 mMs for iGd-TMV. This equates to T values of ~ 30,000 mMs and ~ 35,000 mMs per eGd-TMV and iGd-TMV nanoparticle. Further, we show that interior-labeled TMV rods can undergo thermal transition to form 170 nm-sized spherical nanoparticles containing ~ 25,000 Gd chelates and a per particle relaxivity of almost 400,000 mMs (15.2 mMs per Gd). This work lays the foundation for the use of TMV as a contrast agent for MRI.
为了弥补磁共振成像（MRI）灵敏度较低的问题，人们已开发出纳米颗粒，用于将高负载量的造影剂输送到疾病部位。在此，我们报告了使用植物病毒纳米颗粒烟草花叶病毒（TMV）开发超分子MRI造影剂的情况。分别在内部（iGd-TMV）或外部（eGd-TMV）表面选择性地装载了多达3500个或2000个螯合顺磁性钆（III）离子的棒状TMV纳米颗粒，其尺寸为300×18纳米。通过靶向溶剂暴露的TMV外部或内部表面上的酪氨酸或羧酸侧链来实现空间控制。每个钆离子的离子弛豫率（在60兆赫兹时）从游离Gd（DOTA）的4.9毫摩尔每秒增加到eGd-TMV的18.4毫摩尔每秒和iGd-TMV的10.7毫摩尔每秒。这相当于每个eGd-TMV和iGd-TMV纳米颗粒的弛豫时间值约为30,000毫摩尔每秒和35,000毫摩尔每秒。此外，我们表明内部标记的TMV棒可以发生热转变，形成含有约25,000个钆螯合物且每个颗粒弛豫率几乎为400,000毫摩尔每秒（每个钆为15.2毫摩尔每秒）的170纳米大小的球形纳米颗粒。这项工作为将TMV用作MRI造影剂奠定了基础。
