Nucleus‐Targeted Organoiridium–Albumin Conjugate for Photodynamic Cancer Therapy

• Published in: Angewandte Chemie International Edition Vol. 58; no. 8; pp. 2350 - 2354
• Main Authors: Zhang, Pingyu, Huang, Huaiyi, Banerjee, Samya, Clarkson, Guy J., Ge, Chen, Imberti, Cinzia, Sadler, Peter J.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 18.02.2019; John Wiley and Sons Inc
• Edition: International ed. in English
• Subjects: A549 Cells; Albumin; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cancer; Cancer therapies; Cell Nucleus - drug effects; Cell Proliferation - drug effects; Chemical synthesis; Communication; Communications; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Cytotoxicity; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Human serum albumin; Humans; Iridium - chemistry; Iridium - pharmacology; Irradiation; Models, Molecular; Molecular Structure; Nuclei (cytology); Optical Imaging; organoiridium; Phosphorescence; Photochemotherapy; Photodynamic therapy; photosensitizers; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Radiation; Serum albumin; Serum Albumin, Human - chemistry; Serum Albumin, Human - metabolism; Spheroids; Structure-Activity Relationship; Toxicity; Tumor cell lines; photosensitizers; organoiridium; photodynamic therapy; albumin
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201813002

An organoiridium–albumin bioconjugate (Ir1‐HSA) was synthesized by reaction of a pendant maleimide ligand with human serum albumin. The phosphorescence of Ir1‐HSA was enhanced significantly compared to parent complex Ir1. The long phosphorescence lifetime and high 1O2 quantum yield of Ir1‐HSA are highly favorable properties for photodynamic therapy. Ir1‐HSA mainly accumulated in the nucleus of living cancer cells and showed remarkable photocytotoxicity against a range of cancer cell lines and tumor spheroids (light IC50; 0.8–5 μm, photo‐cytotoxicity index PI=40–60), while remaining non‐toxic to normal cells and normal cell spheroids, even after photo‐irradiation. This nucleus‐targeting organoiridium‐albumin is a strong candidate photosensitizer for anticancer photodynamic therapy. On target: A nucleus‐targeted organo‐iridium‐HSA conjugate for photodynamic therapy has been developed. Phosphorescence of a weakly emissive maleimide‐functionalized Ir complex is greatly enhanced when conjugated to human serum albumin. The iridium‐HSA conjugate targets the nucleus and generates 1O2 for photodynamic therapy upon irradiation with visible light.