Rationally Designed Ir(III) Complex with an Exceptionally Strong Binding to Human Serum Albumin for Targeted Photodynamic Therapy

The application of iridium(III) complexes in photodynamic therapy (PDT) is often limited by their poor selectivity for cancerous cells, necessitating high drug doses that increase the risk of side effects. The development of efficient drug delivery systems such as albumin conjugation is therefore crucial to enhance the tumor-targeted delivery of photosensitizers. To date, the vast majority of metal complexes exhibit weak to moderate binding with human serum albumin, limiting the feasibility of this approach. To overcome this limitation, the rational design through molecular docking and density functional theory calculations of a novel Ir(III) complex as a strong albumin-binding photosensitizer is described. The herein reported compound has the highest albumin binding constant ever reported for an iridium complex, and it showed to photocatalytically produce reactive oxygen species upon blue light irradiation. The presented compound as well as structural derivatives could have high potential in tumor-targeted photodynamic therapy.