Abstract：
Hepatocellular carcinoma (HCC) is a major contributor to global mortality rates, but current treatment options have limitations. Advanced theranostics are needed to effectively integrate diagnosis and therapeutic of HCC. Glycyrrhetinic acid (GA) has abundant binding sites with glycyrrhetinic acid receptors (GA-Rs) on the surface of HCC cells and has also been reported to possess ligands with mitochondrial-targeting capability but with limited efficacy. Herein, we report a near-infrared (NIR) luminescent theranostic complex 1 through conjugating an iridium(III) complex to GA, which exhibits the desired photophysical properties and promotes mitochondrial-targeting capability. Complex 1 was selectively taken up by HepG2 liver cancer cells and was imaged within mitochondria with NIR emission. Complex 1 targeted mitochondria and opened mitochondrial permeability transition pores (MPTPs), resulting in ROS accumulation, mitochondrial damage, disruption of Bax/Bcl-2 equilibrium, and tumor cell apoptosis, resulting in significantly improved anticancer activity compared to GA. This work offers a methodology for developing multifunctional theranostic probes with amplified specificity and efficacy.
摘要：
肝细胞癌（HCC）是全球死亡率的主要贡献者，但目前的治疗方案有局限性.需要先进的治疗药物来有效地整合HCC的诊断和治疗。甘草次酸（GA）在HCC细胞表面具有丰富的与甘草次酸受体（GA-R）的结合位点，并且也有报道具有线粒体靶向能力但功效有限的配体。在这里，我们通过将铱（III）络合物与GA共轭，报告了近红外（NIR）发光的热酸络合物1，其表现出期望的光物理性质并促进线粒体靶向能力。复合物1被HepG2肝癌细胞选择性吸收，并在线粒体内以NIR发射成像。复合物1靶向线粒体和开放的线粒体通透性过渡孔（MPTP），导致ROS积累，线粒体损伤，破坏Bax/Bcl-2平衡，和肿瘤细胞凋亡，导致与GA相比显著改善的抗癌活性。这项工作提供了一种开发具有扩增特异性和功效的多功能治疗诊断探针的方法。
