Chemistry and Biochemistry Department and Center for Bio-Inspired Nanomaterials, Montana State University, Bozeman, Montana 59717, United States.
Mol Pharm. 2013 Jan 7;10(1):11-7. doi: 10.1021/mp300208g. Epub 2012 Jul 16.
Attachment of multiple chelated Gd(3+) ions to the interior of bacteriophage P22 viral capsids affords nanoscale MRI contrast agents with extremely high relaxivity values. Highly fenestrated "wiffleball" morphology is unique to P22 and assures water exchange between the environment and interior cavity of the capsid. The cavity of P22 "wiffleball" was functionalized with a branched oligomer comprising multiple DTPA-Gd complexes resulting in an impressive payload of 1,900 Gd(3+) ions inside each 64 nm capsid. High relaxivities of r(1,ionic) = 21.7 mM(-1) s(-1) and r(1,particle) = 41,300 mM(-1) s(-1) at 298 K, 0.65 T (28 MHz) are reported, with r(1)/r(2) ratio of 0.80 and optimized rotational correlation time for this system. Specific design modifications are suggested for future improvements of viral capsid-based MRI contrast agents directed toward clinical translation.
多个螯合的 Gd(3+) 离子与噬菌体 P22 病毒衣壳的内部结合，提供了具有极高弛豫率值的纳米级 MRI 对比剂。高度有孔的“wiffleball”形态是 P22 所特有的，并确保了衣壳内部腔室与环境之间的水交换。P22“wiffleball”的腔室用包含多个 DTPA-Gd 配合物的支化寡聚物进行功能化，导致每个 64nm 衣壳内有 1900 个 Gd(3+) 离子的惊人载量。在 298 K、0.65 T（28 MHz）下，报道了 r(1,ionic) = 21.7 mM(-1) s(-1) 和 r(1,particle) = 41,300 mM(-1) s(-1) 的高弛豫率，该系统的 r(1)/r(2) 比值为 0.80，旋转相关时间得到优化。针对未来临床转化，针对病毒衣壳基 MRI 对比剂的特定设计改进提出了建议。
