A Ru() complex-based COX-2 targeting type I photosensitizer evokes ferroptosis and apoptosis

• Published in: Chemical communications (Cambridge, England) England), 2024-11, Vol.6 (89), p.1391-1394
• Main Authors: Qi, Fen, Zheng, Xiaoxue, Wu, Yanping, Li, Shumeng, Yao, Shankun, He, Weijiang, Chen, Yuncong, Guo, Zijian
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Cyclooxygenase 2 - metabolism; Drug Screening Assays, Antitumor; Ferroptosis - drug effects; Humans; Mice; Molecular Structure; Oxygen; Photochemotherapy; Photosensitizing Agents - chemical synthesis; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Ruthenium - chemistry; Ruthenium - pharmacology; Ruthenium compounds; Tumors
• ISSN: 1359-7345; 1364-548X; 1364-548X
• DOI: 10.1039/d4cc04217d

Photodynamic therapy (PDT) often faces challenges such as oxygen dependence and limited tumour specificity. We report a tumour-targeting photosensitizer (PS), RuCXB, which enhances uptake by cancer cells by targeting overexpressed cyclooxygenase-2 enzyme in tumours. RuCXB also reduces oxygen dependence via a type I PDT mechanism and achieves a strong therapeutic effect through the synergistic induction of ferroptosis and apoptosis. This work presents a reliable strategy for developing potent PSs with enhanced PDT efficacy, tumour selectivity, and diminished oxygen dependence. A COX-2 targeting type I photosensitizer (PS) RuCXB with improved targetability to cancer cells was developed, which showed less O 2 -dependence and realized high PDT therapeutic effect via the synergism of ferroptosis and apoptosis.