Negi Monika, Venkatesh V
Department of Chemistry, Indian Institute of Technology Roorkee Roorkee 247667 Uttarakhand India
Chem Sci. 2025 Mar 5;16(15):6376-6382. doi: 10.1039/d5sc00156k. eCollection 2025 Apr 9.
Near-infrared (NIR) light-activatable photosensitizers (PSs) have garnered tremendous interest as PSs for photodynamic therapy (PDT) due to the deeper tissue penetration ability and lower toxicity of NIR radiation. However, the low reactive oxygen species (ROS) production, poor tumor accumulation, and residual toxicity of these PSs pose major challenges for further development in this regime. In this regard, we have meticulously designed and synthesized two novel mitochondria-targeting iridium(iii)-dithiocarbamate-cyanine complexes, Ir1@hcy and Ir2@hcy. In particular, Ir2@hcy exhibited both type I and type II PDT with excellent singlet oxygen (O) and hydroxyl radical (˙OH) generation ability under 637 nm/808 nm irradiation, even at an ultra-low power intensity (2 mW cm). Under higher-power irradiation (100 mW cm), the reactive oxygen species (ROS) production by Ir2@hcy was augmented. The elevated levels of ROS caused the disintegration of Ir2@hcy to produce cytotoxic oxindole scaffolds through the dioxetane mechanism. The synergistic production of ROS and cytotoxic species effectively induced mitochondria-mediated cancer cell death in both and 3D tumor spheroid models, offering a new avenue to develop combinational phototherapy (PDT + PACT) for cancer treatment with spatio-temporal precision.
近红外（NIR）光可激活的光敏剂（PSs）因近红外辐射具有更深的组织穿透能力和更低的毒性，作为光动力疗法（PDT）的光敏剂而备受关注。然而，这些光敏剂产生的活性氧（ROS）水平低、肿瘤蓄积性差以及存在残留毒性，给该领域的进一步发展带来了重大挑战。在这方面，我们精心设计并合成了两种新型的靶向线粒体的铱（III）-二硫代氨基甲酸盐-花菁配合物，即Ir1@hcy和Ir2@hcy。特别地，Ir2@hcy在637 nm/808 nm照射下，即使在超低功率强度（2 mW/cm²）下，也表现出I型和II型光动力疗法，具有优异的单线态氧（O₂）和羟基自由基（˙OH）生成能力。在更高功率照射（100 mW/cm²）下，Ir2@hcy产生的活性氧（ROS）增加。ROS水平的升高导致Ir2@hcy分解，通过二氧杂环丁烷机制产生细胞毒性的氧化吲哚支架。ROS和细胞毒性物质的协同产生在二维和三维肿瘤球体模型中均有效地诱导了线粒体介导的癌细胞死亡，为开发具有时空精确性的联合光疗（光动力疗法+光声化疗）用于癌症治疗提供了一条新途径。
