Citation: Panpan Wang, Hongbao Fang, Mengmeng Wang, Guandong Zhang, Na Xu, Yan Su, Hongke Liu, Zhi Su. A mitochondria targeting Ir(III) complex triggers ferroptosis and autophagy for cancer therapy: A case of aggregation enhanced PDT strategy for metal complexes[J]. Chinese Chemical Letters, ;2025, 36(1): 110099. doi: 10.1016/j.cclet.2024.110099 shu

A mitochondria targeting Ir(III) complex triggers ferroptosis and autophagy for cancer therapy: A case of aggregation enhanced PDT strategy for metal complexes

Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China

fanghb@njnu.edu.cn

suyanahnu@163.com

zhisu@njnu.edu.cn

Received Date: 29 March 2024
Revised Date: 4 June 2024
Accepted Date: 6 June 2024
Available Online: 6 June 2024

Figures(5)

Metal complexes hold significant promise in tumor diagnosis and treatment. However, their potential applications in photodynamic therapy (PDT) are hindered by issues such as poor photostability, low yield of reactive oxygen species (ROS), and aggregation-induced ROS quenching. To address these challenges, we present a molecular self-assembly strategy utilizing aggregation-induced emission (AIE) conjugates for metal complexes. As a proof of concept, we synthesized a mitochondrial-targeting cyclometalated Ir(III) photosensitizer Ir-TPE. This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups. Ir-TPE readily self-assembles into nanoaggregates in aqueous solution, leading to a significant production of ROS upon light irradiation. Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria, resulting in mitochondrial DNA damage. This damage can lead to ferroptosis and autophagy, two forms of cell death that are highly cytotoxic to cancer cells. The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS, leading to a more pronounced cytotoxic effect. In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication. This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.
- Metal complex,
- AIEgens,
- Mitochondria targeting,
- Enhanced photodynamic therapy,
- Anticancer agent
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