A tricarbonyl rhenium(I) complex decorated with boron dipyrromethene for endoplasmic reticulum-targeted photodynamic therapy

Organelle-targeted photodynamic therapy (PDT) has recently emerged as a promising strategy for developing effective and precise cancer therapy. Selective generation of highly cytotoxic reactive oxygen species (ROS) in the endoplasmic reticulum (ER) region by PDT can effectively kill cancer cells. In this work, an ER-targeted tricarbonyl Re(I) complex (Re-BDP) was designed and synthesized by combining a tricarbonyl Re(I) unit and a photoactive boron dipyrromethene (BODIPY) chromophore moiety. Complex Re-BDP was characterized by ESI-MS, H-1 NMR spectroscopy, FT-IR spectroscopy, and high-performance liquid chromatography (HPLC). The complex displayed strong absorbance (epsilon = 6.56 x 10(4)/M-1 cm(-1) in CH2Cl2) in the visible light region (similar to 512 nm) and a high singlet oxygen quantum yield (phi(Delta) = 0.89 in methanol). Co-localization assays revealed that it accumulated preferentially in the ER. Complex Re-BDP exhibited high phototoxicity upon visible light (525 nm) irradiation toward human cervical cancer HeLa, human lung cancer A549 and human breast cancer MDA-MB-231 cells. Mechanism experiments showed that complex Re-BDP caused reactive oxygen species (ROS) generation and induced ER stress in HeLa cells upon light irradiation, leading to caspase-dependent apoptosis, accompanied by mitochondrial dysfunction. Overall, the results demonstrate that complex Re-BDP is a promising phototherapeutic agent for ER-targeted cancer phototherapy. This work highlights the effectiveness of developing efficient organelle-targeted metal-based phototherapeutic agents by appropriate conjugation of metal complexes and organic chromophores.