Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors.
Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors.
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DOI：
10.1021/acscentsci.7b00253
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发表时间：
2017-07-26
影响因子：
18.2
通讯作者：
Johnson JA
中科院分区：
文献类型：
--
作者：
Nguyen HV;Chen Q;Paletta JT;Harvey P;Jiang Y;Zhang H;Boska MD;Ottaviani MF;Jasanoff A;Rajca A;Johnson JA
无金属磁共振成像 (MRI) 药物可以克服某些患者群体中与金属药物相关的已知毒性，并实现体内功能性 MRI 的新模式。在此，我们报道了硝基氧功能化的刷臂星形聚合物有机自由基造影剂（BASP-ORCA），它克服了基于硝基氧的MRI造影剂的低对比度和较差的体内稳定性。由于其独特的纳米结构，BASP-ORCA 的过硝基氧横向弛豫率比普通硝基氧高出约 44 倍，在高还原性环境中具有出色的稳定性，并且毒性低。这些特征相结合，在全身给药后长达 20 小时内，BASP-ORCA 在小鼠皮下肿瘤中积累足够浓度，从而观察到与金属制剂相同的 MRI 对比度。据我们所知，BASP-ORCA 是第一种能够使用临床高场 1H MRI 技术长时间进行肿瘤成像的硝基氧 MRI 造影剂。基于硝基氧化物的刷臂星形聚合物有机自由基造影剂（冲臂星形聚合物有机自由基造影剂）具有高横向弛豫性和抗还原稳定性，可在全身给药20小时后对小鼠肿瘤进行无金属体内磁共振成像。
Metal-free magnetic resonance imaging (MRI) agents could overcome the established toxicity associated with metal-based agents in some patient populations and enable new modes of functional MRI in vivo. Herein, we report nitroxide-functionalized brush-arm star polymer organic radical contrast agents (BASP-ORCAs) that overcome the low contrast and poor in vivo stability associated with nitroxide-based MRI contrast agents. As a consequence of their unique nanoarchitectures, BASP-ORCAs possess per-nitroxide transverse relaxivities up to ∼44-fold greater than common nitroxides, exceptional stability in highly reducing environments, and low toxicity. These features combine to provide for accumulation of a sufficient concentration of BASP-ORCA in murine subcutaneous tumors up to 20 h following systemic administration such that MRI contrast on par with metal-based agents is observed. BASP-ORCAs are, to our knowledge, the first nitroxide MRI contrast agents capable of tumor imaging over long time periods using clinical high-field 1H MRI techniques. Nitroxide-based brush-arm star-polymer organic radical contrast agents—rush-arm star polymer organic radical contrast agents—display high transverse relaxivity and stability against reduction, which enables metal-free in vivo magnetic resonance imaging of tumors in mice 20 h following systemic administration.
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使用大量硝化氧化物对细胞氧化应激进行两光子荧光显微镜成像。
影响因子：
15
作者：
Ahn, Hyo-Yang;Fairfull-Smith, Kathryn E.;Morrow, Benjamin J.;Lussini, Vanessa;Kim, Bosung;Bondar, Mykhailo V.;Bottle, Steven E.;Belfield, Kevin D.
通讯作者：
Belfield, Kevin D.
影响因子：
3.4
作者：
Chapman, Kathryn;Sewell, Fiona;Robinson, Sally
通讯作者：
Robinson, Sally
影响因子：
10.8
作者：
Detappe, Alexandre;Kunjachan, Sijumon;Berbeco, Ross
通讯作者：
Berbeco, Ross
影响因子：
15
作者：
Chou, Shang-Wei;Shau, Yu-Hong;Chen, Chia-Chun
通讯作者：
Chen, Chia-Chun
影响因子：
5.5
作者：
Burts, Alan O.;Li, Yongjun;Johnson, Jeremiah A.
通讯作者：
Johnson, Jeremiah A.