Iridium Complex Probes for Monitoring of Cellular Oxygen Levels and Imaging of Hypoxic Tissues
Iridium Complex Probes for Monitoring of Cellular Oxygen Levels and Imaging of Hypoxic Tissues
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用于监测细胞氧水平和缺氧组织成像的铱复合物探针
DOI：
10.1117/12.910170
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
S.
中科院分区：
文献类型：
--
作者：
Yoshihara;T.;Kobayashi;A.;Oda;M.;Hosaka;M.;Takeuchi;T.;Tobita;S.
我们最近报道了一种发红光的铱络合物 (btp)2Ir (acac) (BTP) 作为活体小鼠肿瘤成像的缺氧传感探针。 BTP 表现出对氧敏感的磷光，可用于监测活细胞中的氧气水平并可视化缺氧组织。为了提高BTP的组织渗透性，我们通过两种不同的方法设计并合成了近红外发射铱配合物：在BTP中延伸苯并噻吩基吡啶基配体的π-共轭体系以及在配体的合适位置引入取代基。前一种方法是成功的，并且在不降低发射量子产率的情况下获得了近红外发射铱配合物。通过在乙酰丙酮配体中引入亲水基团，BTP 的细胞摄取大大提高。使用这些改进的探针，进行了体内寿命测量，以证实 SCC-7 荷瘤小鼠肿瘤组织的缺氧。使用 Nd3+:YAG 激光的二次谐波（532 nm）激发组织中的铱配合物，并使用时间相关单光子计数技术测量磷光寿命。与正常组织发出的磷光相比，肿瘤区域发出的磷光实际上具有更长的寿命，这证明了肿瘤组织的缺氧性质。
We have recently reported that a red-emitting iridium complex (btp)2Ir (acac) (BTP) serves as a hypoxia-sensing probe for tumor imaging in living mice. BTP exhibits oxygen-sensitive phosphorescence that can be utilized to monitor oxygen levels in living cells and to visualize hypoxic tissues. To improve the tissue penetrance of BTP, we designed and synthesized near-IR emitting iridium complexes by two different approaches: extension of the π- conjugated system of benzothienyl-pyridinato ligand in BTP and introduction of substituents into suitable positions of ligands. The former approach was successful, and near-IR emitting iridium complexes were obtained without reduction in the emission quantum yield. Cellular uptake of BTP was greatly improved by introducing a hydrophilic group into the acetylacetonato ligand. Using these improved probes, in-vivo lifetime measurements were made to substantiate the hypoxia of tumor tissues in SCC-7 tumor-bearing mice. The second-harmonic (532 nm) of Nd3+:YAG laser was used to excite iridium complexes in tissues, and the phosphorescence lifetime was measured using the time-correlated single photon counting technique. The phosphorescence emitted from the tumor region actually gave longer lifetimes compared to those emitted from the normal tissues, demonstrating the hypoxic nature of tumor tissues.