Leveraging Tumor Microenvironment to Boost Synergistic Photodynamic Therapy, Ferroptosis Anti‐Tumor Efficiency Based on a Functional Iridium(III) Complex

Pei, Yu; Pan, Yinzhen; Zhang, Zhijun; Zhu, Jun; Sun, Yan; Zhang, Qian; Zhu, Dongxia; Li, Guangzhe; Bryce, Martin R.; Wang, Dong; Tang, Ben Zhong

Abstract

The tumor microenvironment (TME) severely limits the efficacy of clinical applications of photodynamic therapy (PDT). The development of a functional agent allowing full use of the TME to boost synergistic PDT and ferroptosis anti‐tumor efficiency is an appealing yet significantly challenging task. Herein, to overcome the adverse influence on PDT of hypoxia and high level of glutathione (GSH) in the TME, an imine bond is introduced into an Ir(III)‐ferrocene complex to construct a small molecule drug, named Ir‐Fc, for tumors’ imaging and therapy. The cleavage of the imine bond in the lysosome effectively disrupts the photoinduced electron transfer (PET) process, realizing the decomposition of Ir‐Fc into Fc‐CHO and Ir‐NH2. Fc‐CHO produces •OH by Fenton reactions under dark conditions and induces ferroptosis in tumor cells, and Ir‐NH2 shows prominent performance for type‐I and type‐II reactive oxygen species (ROS) production. Meanwhile, the ferroptosis pathway simultaneously consumes large amounts of GSH and produces O2 for effectively relieving hypoxia. These distinctive outputs make Ir‐Fc an exceptional molecule for effective tumor synergistic therapy. This study thus brings a new and revolutionary PDT protocol for practical cancer treatment.

Citation

Pei, Y., Pan, Y., Zhang, Z., Zhu, J., Sun, Y., Zhang, Q., Zhu, D., Li, G., Bryce, M. R., Wang, D., & Tang, B. Z. (online). Leveraging Tumor Microenvironment to Boost Synergistic Photodynamic Therapy, Ferroptosis Anti‐Tumor Efficiency Based on a Functional Iridium(III) Complex. Advanced Science, Article 2413879. https://doi.org/10.1002/advs.202413879

• Journal Article Type: Article
• Acceptance Date: Jan 26, 2025
• Online Publication Date: Feb 14, 2025
• Deposit Date: Mar 14, 2025
• Publicly Available Date: Mar 14, 2025
• Journal: Advanced Science
• Electronic ISSN: 2198-3844
• Publisher: Wiley Open Access
• Peer Reviewed: Peer Reviewed
• Article Number: 2413879
• DOI: https://doi.org/10.1002/advs.202413879
• Keywords: Fenton reaction, ferroptosis, ferrocene, iridium(III) complex, photodynamic therapy
• Public URL: https://durham-repository.worktribe.com/output/3482396