Self-Chemiluminescence-Triggered Ir(III) Complex Photosensitizer for Photodynamic Therapy against Hypoxic Tumor

Liu, Shengnan; Chen, Haoran; Wu, Qi; Sun, Yan; Pei, Yu; Wang, Ziwei; Zhu, Dongxia; Li, Gungzhe; Bryce, Martin R.; Chang, Yulei

Abstract

The limited optical penetration depth and hypoxic tumor microenvironment (TME) are key factors that hinder the practical applications of conventional photodynamic therapy (PDT). To fundamentally address these issues, self-luminescent photosensitizers (PSs) can achieve efficient PDT. Herein, a self-chemiluminescence (CL)-triggered Ir complex PS, namely, , with low-O -dependence type I photochemical processes is reported for efficient PDT. The rational design achieves efficient chemiluminescence resonance energy transfer (CRET) from covalently bonded luminol units to the Ir complex in under the catalysis of H O and hemoglobin (Hb) to generate O and O . Liposome nanoparticles (NPs) are constructed by loading and Hb. The intracellular H O and loaded Hb catalyze the luminol part of , and the part is then excited to produce types I and II reactive oxygen species (ROS) through CRET, inducing cell death, even under hypoxic conditions, and promoting cell apoptosis. is used for tumor imaging and inhibits tumor growth in 4T1-bearing mouse models through intratumoral injection without external light sources. This work provides new designs for transition metal complex PSs that conquer the limitations of external light sources and the hypoxic TME in PDT.

Citation

Liu, S., Chen, H., Wu, Q., Sun, Y., Pei, Y., Wang, Z., Zhu, D., Li, G., Bryce, M. R., & Chang, Y. (2024). Self-Chemiluminescence-Triggered Ir(III) Complex Photosensitizer for Photodynamic Therapy against Hypoxic Tumor. Inorganic Chemistry, 63(35), 16404-16417. https://doi.org/10.1021/acs.inorgchem.4c02399

• Journal Article Type: Article
• Acceptance Date: Aug 7, 2024
• Online Publication Date: Aug 16, 2024
• Publication Date: Sep 2, 2024
• Deposit Date: Aug 19, 2024
• Publicly Available Date: Aug 19, 2024
• Journal: Inorganic Chemistry
• Print ISSN: 0020-1669
• Electronic ISSN: 1520-510X
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 63
• Issue: 35
• Pages: 16404-16417
• DOI: https://doi.org/10.1021/acs.inorgchem.4c02399
• Public URL: https://durham-repository.worktribe.com/output/2761985