Membrane-Permeable Mn(III) Complexes for Molecular Magnetic Resonance Imaging of Intracellular Targets.
Membrane-Permeable Mn(III) Complexes for Molecular Magnetic Resonance Imaging of Intracellular Targets.
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DOI：
10.1021/jacs.5b13337
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发表时间：
2016-05-04
影响因子：
15
通讯作者：
Jasanoff A
中科院分区：
文献类型：
--
作者：
Barandov A;Bartelle BB;Gonzalez BA;White WL;Lippard SJ;Jasanoff A
细胞内隔室约占身体的三分之二，但将分子成像探针递送到这些空间可能具有挑战性。这种情况对于设计用于通过磁共振成像（MRI）检测的探头尤其如此，MRI是一种高分辨率但相对不敏感的模态。大多数MRI造影剂是极性和膜不渗透性的，使得难以以足够的量递送它们以用于测量细胞内分析物。在这里，我们解决这个问题，通过引入一类新的平面四齿锰（III）螯合物组装从1，2-苯二酰胺（PDA）的骨干。Mn（III）-PDA复合物显示与Gd（III）基造影剂相当的T1弛豫率，并通过确定的机制进行自发的胞质定位。掺入酶可裂解的乙酰甲氧基酯基团的探针变体被细胞内酯酶加工并在细胞中积累。用乙酯修饰的探针优先标记表达底物选择性酯酶的遗传修饰细胞。在每种情况下，造影剂引起了强大的T1加权MRI增强，提供了通过Mn（III）-PDA复合物检测细胞内靶点的先例。因此，这些化合物构成了一个平台，从该平台开发用于细胞内不同过程的分子MRI的试剂。
Intracellular compartments make up roughly two thirds of the body, but delivery of molecular imaging probes to these spaces can be challenging. This situation is particularly true for probes designed for detection by magnetic resonance imaging (MRI), a high resolution but relatively insensitive modality. Most MRI contrast agents are polar and membrane impermeant, making it difficult to deliver them in sufficient quantities for measurement of intracellular analytes. Here we address this problem by introducing a new class of planar tetradentate Mn(III) chelates assembled from a 1,2-phenylenediamido (PDA) backbone. Mn(III)-PDA complexes display T1 relaxivity comparable to that of Gd(III)-based contrast agents and undergo spontaneous cytosolic localization via defined mechanisms. Probe variants incorporating enzyme-cleavable acetomethoxy ester groups are processed by intracellular esterases and accumulate in cells. Probes modified with ethyl esters preferentially label genetically modified cells that express a substrate-selective esterase. In each case, the contrast agents gives rise to robust T1-weighted MRI enhancements, providing precedents for the detection of intracellular targets by Mn(III)-PDA complexes. These compounds therefore constitute a platform from which to develop reagents for molecular MRI of diverse processes inside cells.
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影响因子：
--
作者：
Li Y;Sheth VR;Liu G;Pagel MD
通讯作者：
Pagel MD
DOI：
10.1073/pnas.1111943109
发表时间：
2012-03-27
影响因子：
11.1
作者：
Tian, Lin;Yang, Yunlei;Lavis, Luke D.
通讯作者：
Lavis, Luke D.
DOI：
10.1073/pnas.1319000111
发表时间：
2014-01-07
影响因子：
11.1
作者：
Patrick, P. Stephen;Hammersley, Jayne;Brindle, Kevin M.
通讯作者：
Brindle, Kevin M.
影响因子：
2
作者：
Jobsis, Paul D.;Rothstein, Emily C.;Balaban, Robert S.
通讯作者：
Balaban, Robert S.
影响因子：
4.6
作者：
ROCKLAGE, SM;CACHERIS, WP;RAYMOND, KN
通讯作者：
RAYMOND, KN