Nitroxyl Modified Tobacco Mosaic Virus as a Metal-Free High-Relaxivity MRI and EPR Active Superoxide Sensor.
Nitroxyl Modified Tobacco Mosaic Virus as a Metal-Free High-Relaxivity MRI and EPR Active Superoxide Sensor.
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DOI：
10.1021/acs.molpharmaceut.8b00262
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发表时间：
2018-08-06
影响因子：
4.9
通讯作者：
Gassensmith JJ
中科院分区：
文献类型：
--
作者：
Dharmarwardana M;Martins AF;Chen Z;Palacios PM;Nowak CM;Welch RP;Li S;Luzuriaga MA;Bleris L;Pierce BS;Sherry AD;Gassensmith JJ
已知超氧化物过量产生发生在需要重症监护的多种疾病状态中，但深部组织中超氧化物的非侵入性检测仍然是一个挑战。在此，我们报告了一种无金属磁共振成像（MRI）和电子顺磁共振（EPR）活性造影剂制备的“点击共轭”顺磁性有机自由基造影剂（ORCAs）的烟草花叶病毒（TMV）的表面。虽然已知ORCA在体内被还原为MRI/EPR沉默状态，但它们的氧化特别是由活性氧物质-特别是超氧化物-促进，并且在很大程度上不受过氧化物和分子氧的影响。不幸的是，单分子ORCA通常提供弱的MRI对比度。相反，我们的数据证实，大分子ORCA-TMV缀合物在低场（<3.0T）下显示出T1对比度的显著增强，在高场（9.4T）下显示出T2对比度的显著增强。此外，我们证明了TMV的独特拓扑结构允许用于同时荧光和MRI/EPR成像的“无猝灭荧光”双峰探针，这通过利用TMV纳米颗粒的独特内表面和外表面而成为可能。最后，我们表明TMV-ORCAs对正常的细胞呼吸没有反应，最大限度地减少了背景的可能性，但仍然对复杂的生物液体（如血清）中酶促产生的超氧化物有反应。
Superoxide overproduction is known to occur in multiple disease states requiring critical care yet non-invasive detection of superoxide in deep tissue remains a challenge. Herein, we report a metal-free magnetic resonance imaging (MRI) and electron paramagnetic resonance (EPR) active contrast agent prepared by “click conjugating” paramagnetic organic radical contrast agents (ORCAs) to the surface of tobacco mosaic virus (TMV). While ORCAs are known to be reduced in vivoto an MRI/EPR silent state, their oxidation is facilitated specifically by reactive oxygen species—in particular superoxide—and are largely unaffected by peroxides and molecular oxygen. Unfortunately, single molecule ORCAs typically offer weak MRI contrast. In contrast, our data confirm that the macromolecular ORCA-TMV conjugates show marked enhancement for T1 contrast at low field (<3.0 T), and T2 contrast at high field (9.4 T). Additionally, we demonstrated that the unique topology of TMV allows for “quenchless fluorescent” bimodal probe for concurrent fluorescence and MRI/EPR imaging, which was made possible by exploiting the unique inner and outer surface of the TMV nanoparticle. Finally, we show TMV-ORCAs do not respond to normal cellular respiration, minimizing the likelihood for background, yet still respond to enzymatically produced superoxide in complicated biological fluids like serum.
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影响因子：
3.4
作者：
Do, Quyen N.;Ratnakar, James S.;Kovacs, Zoltan;Sherry, A. Dean
通讯作者：
Sherry, A. Dean
影响因子：
3.2
作者：
Bruckman, Michael A.;Kaur, Gagandeep;Wang, Qian
通讯作者：
Wang, Qian
影响因子：
2.2
作者：
HALLE, B;WENNERSTROM, H
通讯作者：
WENNERSTROM, H
影响因子：
7
作者：
Bruckman, Michael A.;Randolph, Lauren N.;Steinmetz, Nicole F.
通讯作者：
Steinmetz, Nicole F.
DOI：
10.1098/rstb.1999.0403
发表时间：
1999-03-29
期刊：
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
Harrison, BD;Wilson, TMA
通讯作者：
Wilson, TMA