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Updated: Jun 29, 2025
Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Uridine-Modified Ruthenium(II) Complex as Lysosomal LIMP-2 Targeting Photodynamic Therapy Photosensitizer for the
Qiong Wu1,2, Chanling Yuan1, Jiacheng Wang1
1School of Pharmacy, Guangdong Engineering Technology Research Centre of Molecular Probe and Biomedicine Imaging, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Abstract:
Lysosome-targeted photodynamic therapy, which enhances reactive oxygen species (ROS)-responsive tumor cell death, has emerged as a promising strategy for cancer treatment. Herein, a uridine (dU)-modified Ru(II) complex (RdU) was synthesized by click chemistry. It was found that RdU exhibits impressive photo-induced inhibition against the growth of triple-negative breast cancer (TNBC) cells in normoxic and hypoxic microenvironments through ROS production. It was further revealed that RdU induces ferroptosis of MDA-MB-231 cells under light irradiation (650 nm, 300 mW/cm2). Additional experiments showed that RdU binds to lysosomal integral membrane protein 2 (LIMP-2), which was confirmed by the fact that RdU selectively localizes in the lysosomes of MDA-MB-231 cells and significantly augments the levels of LIMP-2. Molecular docking simulations and an isothermal titration calorimetry assay also showed that RdU has a high affinity to LIMP-2. Finally, in vivo studies in tumor-bearing (MDA-MB-231 cells) nude mice showed that RdU exerts promising photodynamic therapeutic effects on TNBC tumors. In summary, the uridine-modified Ru(II) complex has been developed as a potential LIMP-2 targeting agent for TNBC treatment through enhancing ROS production and promoting ferroptosis.
