Magnetic resonance contrast agents from viral capsid shells: A comparison of exterior and interior cargo strategies
Magnetic resonance contrast agents from viral capsid shells: A comparison of exterior and interior cargo strategies
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DOI：
10.1021/nl070512c
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发表时间：
2007-08-01
期刊：
影响因子：
10.8
通讯作者：
Francis, Matthew B.
中科院分区：
文献类型：
--
作者：
Hooker, Jacob M.;Datta, Ankona;Francis, Matthew B.
以噬菌体MS2作为生物分子支架构建了两种高弛豫率的纳米级磁共振造影剂。蛋白质衣壳外壳在其外表面或内表面进行功能化，以展示多个醛官能团。随后，通过肟缩合反应将约90个异足双（羟基吡啶酮）对苯二甲酰胺配体连接到这些位点。在与Gd³⁺络合后，产生了离子弛豫率高达41.6 mM⁻¹ s⁻¹（30 MHz，25℃）以及总分子弛豫率高达3900 mM⁻¹ s⁻¹（30 MHz，25℃）的造影剂。将Gd - 螯合物隔离在内表面（通过酪氨酸残基连接）的衣壳不仅比其外表面功能化的对应物（依靠赖氨酸修饰）具有更高的弛豫率，而且还表现出更好的水溶性和衣壳稳定性。将功能性货物连接到内表面预计可将其对生物分布的影响降至最低，这对于通过连接在衣壳外表面的其他基团进行组织靶向具有显著优势。
Two high-relaxivity nanoscale magnetic resonance contrast agents have been built using bacteriophage MS2 as a biomolecular scaffold. Protein capsid shells were functionalized on either the exterior or interior surface to display multiple copies of an aldehyde functional group. Subsequently, similar to 90 heteropodal bis(hydroxypyridonate)terephthalamide ligands were attached to these sites through oxime condensation reactions. Upon complexation with Gd3+, contrast agents with ionic relaxivities of up to 41.6 mM(-1) s(-1) (30 MHz, 25 degrees C) and total molecular relaxivities of up to 3900 mM(-1) s(-1) (30 MHz, 25 degrees C) were produced. Capsids sequestering the Gd-chelates on the interior surface (attached through tyrosine residues) not only provided higher relaxivities than their exterior functionalized counterparts (which relied on lysine modification) but also exhibited improved water solubility and capsid stability. The attachment functional cargo to the interior surface is envisioned to minimize its influences on biodistribution, yielding significant advantages for tissue targeting by additional groups attached to the capsid exterior.