2. Academic Validation
  3. A glycyrrhetinic acid-iridium(III) conjugate as a theranostic NIR probe for hepatocellular carcinoma with mitochondrial-targeting ability

A glycyrrhetinic acid-iridium(III) conjugate as a theranostic NIR probe for hepatocellular carcinoma with mitochondrial-targeting ability

  • Eur J Med Chem. 2023 Nov 25:264:115995. doi: 10.1016/j.ejmech.2023.115995.
Ling Wang 1,  Xueliang Wang 2,  Feng Chen 1,  Ying-Qi Song 1,  Sang-Cuo Nao 1,  Daniel Shiu-Hin Chan 3,  Chun-Yuen Wong 3,  Wanhe Wang 4,  Chung-Hang Leung 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, China.
  • 2 Institute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, Shaanxi, 710072, China; Research & Development Institute of Northwestern Polytechnical University in Shenzhen, 45 South Gaoxin Road, Shenzhen, 518057, China.
  • 3 Department of Chemistry, City University of Hong Kong, Hong Kong, 999077, China.
  • 4 Institute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, Shaanxi, 710072, China; Research & Development Institute of Northwestern Polytechnical University in Shenzhen, 45 South Gaoxin Road, Shenzhen, 518057, China. Electronic address: [email protected].
  • 5 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, China; Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Macao, 999078, China; Macau Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, 999078, China; MoE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macao, 999078, China. Electronic address: [email protected].
PMID: 38043488 DOI: 10.1016/j.ejmech.2023.115995
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.

Keywords

Glycyrrhetinic acid (GA); Hepatocellular carcinoma; Iridium(III) complex; Mitochondrial targeting; NIR imaging; Theranostic.

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