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.

铱(III)配合物（iridium(III) complexes）在光动力治疗（photodynamic therapy, PDT）中的应用常受限于其对癌细胞的选择性不足，需采用较高药物剂量，进而提升了副作用发生风险。因此，开发白蛋白结合等高效药物递送系统，对增强光敏剂的肿瘤靶向递送能力至关重要。迄今为止，绝大多数金属配合物与人血清白蛋白（human serum albumin）的结合能力仅为弱至中等，限制了该策略的可行性。为克服这一局限，本文报道了一种通过分子对接与密度泛函理论计算理性设计的、可与人血清白蛋白强力结合的新型Ir(III)配合物光敏剂。该化合物拥有目前已报道铱配合物中最高的白蛋白结合常数，且被证实在蓝光照射下可光催化产生活性氧物种（reactive oxygen species）。该化合物及其结构衍生物在肿瘤靶向光动力治疗中具备极高的应用潜力。