Engineered Nonviral Protein Cages Modified for MR Imaging.
Engineered Nonviral Protein Cages Modified for MR Imaging.
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DOI：
10.1021/acsabm.2c00892
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发表时间：
2023-02-20
影响因子：
4.7
通讯作者：
Meade, Thomas J
中科院分区：
文献类型：
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作者：
Kaster, Megan A;Levasseur, Mikail D;Edwardson, Thomas G W;Caldwell, Michael A;Hofmann, Daniela;Licciardi, Giulia;Parigi, Giacomo;Luchinat, Claudio;Hilvert, Donald;Meade, Thomas J
医学诊断成像利用磁共振（MR）在单次扫描中提供解剖学、功能学和分子信息。纳米粒子通常用钆（III）配合物标记，以增强造影剂（CAs）的MR信号，使其具有大负载量和高质子弛豫效率（弛豫率，r1）。本研究检测了两种结构独特的笼状物AaLS - 13和OP（用钆（III）标记）的MR性能。这些笼状物具有与治疗诊断平台开发相关的特性，包括：（i）明确的结构、对称性和尺寸；（ii）易于进行大量工程改造；（iii）可调节治疗相关货物分子的负载量；（iv）高物理稳定性；（v）通过微生物发酵易于制造。与单独的钆（III）配合物（r1 = 4 mM⁻¹ s⁻¹）相比，所得的结合物显示出显著增强的质子弛豫率（在1.4 T时，r1 = 11 - 18 mM⁻¹ s⁻¹）。血清体模图像显示，钆（III）标记的AaLS - 13和OP笼状物的对比度分别增强了107%和57%。此外，质子核磁共振弛豫分散（¹H NMRD）曲线显示最大弛豫率值为50 mM⁻¹ s⁻¹。对¹H NMRD曲线的最佳拟合分析将钆（III）标记笼状物的高弛豫率归因于结合物的分子缓慢翻滚以及结合的钆（III）配合物的局部运动受限。
Diagnostic medical imaging utilizes magnetic resonance (MR) to provide anatomical, functional, and molecular information in a single scan. Nanoparticles are often labeled with Gd(III) complexes to amplify the MR signal of contrast agents (CAs) with large payloads and high proton relaxation efficiencies (relaxivity, r1). This study examined the MR performance of two structurally unique cages, AaLS-13 and OP, labeled with Gd(III). The cages have characteristics relevant for the development of theranostic platforms, including (i) well-defined structure, symmetry, and size; (ii) the amenability to extensive engineering; (iii) the adjustable loading of therapeutically relevant cargo molecules; (iv) high physical stability; and (v) facile manufacturing by microbial fermentation. The resulting conjugates showed significantly enhanced proton relaxivity (r1 = 11–18 mM–1 s–1 at 1.4 T) compared to the Gd(III) complex alone (r1 = 4 mM–1 s–1). Serum phantom images revealed 107% and 57% contrast enhancements for Gd(III)-labeled AaLS-13 and OP cages, respectively. Moreover, proton nuclear magnetic relaxation dispersion (1H NMRD) profiles showed maximum relaxivity values of 50 mM–1 s–1. Best-fit analyses of the 1H NMRD profiles attributed the high relaxivity of the Gd(III)-labeled cages to the slow molecular tumbling of the conjugates and restricted local motion of the conjugated Gd(III) complex.
影响因子：
10.8
作者：
Liepold LO;Abedin MJ;Buckhouse ED;Frank JA;Young MJ;Douglas T
通讯作者：
Douglas T
影响因子：
2.3
作者：
Klemm, Piper J.;Floyd, William C., III;Andolina, Christopher M.;Frechet, Jean M. J.;Raymond, Kenneth N.
通讯作者：
Raymond, Kenneth N.