Amphiphilic Gemini Iridium(111) Complex as a Mitochondria-Targeted Theranostic Agent for Tumor Imaging and Photodynamic Therapy
Amphiphilic Gemini Iridium(111) Complex as a Mitochondria-Targeted Theranostic Agent for Tumor Imaging and Photodynamic Therapy
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两亲性 Gemini Iridium(111) 复合物作为线粒体靶向治疗剂用于肿瘤成像和光动力治疗
DOI：
10.1021/acsami.9b01205
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发表时间：
2019
影响因子：
9.5
通讯作者：
Hou Linxi
中科院分区：
文献类型：
--
作者：
Yi Sili;Lu Zhen;Zhang Jin;Wang Jun;Xie Zenghong;Hou Linxi
肿瘤的临床诊断和治疗因多功能治疗药物的发展而显著受益，多功能治疗药物集肿瘤靶向、成像和治疗于一体。然而，将成像和治疗功能整合到单分子框架中仍然是一个巨大的挑战。本文合成并表征了一类双亲性铱（III）配合物（GIC） Ir1-Ir6。季铵基团的存在使GIC具有可调节的水溶性和优异的自组装性能。光谱和计算结果表明，在环金属化配体（ĈN配体）中引入QA基团可以克服聚集引起的发射猝灭的缺点，确保Ir1-Ir3在水介质中具有高发射强度和优异的单重态氧（1O2）生成能力。基于细胞的实验表明，Ir3具有更高的细胞摄取效率，并且特异性地定位于线粒体，并且具有出色的光稳定性和令人印象深刻的光毒性指数，在肿瘤细胞的线粒体靶向成像和光动力治疗（PDT）中具有令人满意的性能。此外，体内研究进一步证明，Ir3具有良好的抗肿瘤活性，可显著抑制PDT作用下HepG2细胞的生长。因此，该研究为设计具有临床应用潜力的多功能铱复合物治疗药物提供了一个有希望的策略，用于线粒体靶向成像和单分子框架的PDT。
Clinical diagnostics and therapeutics of tumors are significantly benefitted by the development of multifunctional theranostic agents, which integrate tumor targeting, imaging, and therapeutics. However, the integration of imaging and therapy functionalities to a unimolecular framework remains a great challenge. Herein, a family of amphiphilic gemini iridium(III) complexes (GIC), Ir1–Ir6, are synthesized and characterized. The presence of quaternary ammonium (QA) groups endows GIC with adjustable water solubility and excellent self-assembly properties. Spectroscopic and computational results reveal that introducing QA groups into cyclometalating ligands (ĈN ligands) can overcome the drawback of aggregation-caused emission quenching and ensure Ir1–Ir3 with high emission intensity and excellent singlet oxygen (1O2) generation ability in aqueous media. Cell-based assays indicate that Ir3 shows higher cellular uptake efficiency and localizes specifically in the mitochondria, as well as exhibits outstanding photostability and an impressive phototoxicity index with satisfactory performance in mitochondria-targeted imaging and photodynamic therapy (PDT) of tumor cells. Furthermore, in vivo studies further prove that Ir3 possesses excellent antitumor activity and remarkably inhibits the growth of the HepG2 cells under PDT treatment. Consequently, this study presents a promising strategy for designing clinical application potential multifunctional iridium complex theranostic agents for mitochondria-targeted imaging and PDT in a single molecular framework.