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A GSH-responsive Ru(II) complex: Mitochondria-targeted cell imaging and photodynamic therapy
Meihua Chen1, Rui Tu1, Xiangjun Mu1
1Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Key Laboratory of Analysis and Testing Technology for Food Safety and Health, Department of Chemistry, Fuzhou University, Fuzhou, PR China.
Abstract:
Glutathione (GSH) is a critical intracellular antioxidant. In cancer cells, the overexpression of GSH scavenges reactive oxygen species (ROS) produced during photodynamic therapy (PDT), thereby compromising therapeutic efficacy. To address this limitation, we designed and synthesized a GSH-responsive Ru(II) complex (Ru(phen)2(bpy-nap)(PF6)2) for simultaneous GSH imaging and enhanced PDT. This probe exhibits excellent GSH-sensing performance, including a significant phosphorescence turn-on response and a low detection limit (0.05 μM). It was successfully employed for visualizing both endogenous and exogenous GSH in HepG2 cells by imaging. Furthermore, under 450 nm bandpass xenon lamp irradiation, it demonstrates remarkable photostability and generates both Type I and Type II ROS, leading to potent phototoxicity against cancer cells. Notably, the probe selectively localizes in mitochondria, further enhancing its therapeutic potential. Given these advantages, Ru(phen)2(bpy-nap)(PF6)2 represents a promising dual-functional phosphorescence probe for GSH detection and PDT applications.
Insights
This study introduces a novel ruthenium complex that detects glutathione (GSH) and enhances photodynamic therapy (PDT) in cancer cells. The probe offers improved cancer treatment by visualizing GSH and generating reactive oxygen species (ROS) for targeted cell death.
Area of Science:
- Biomedical Engineering
- Chemistry
- Oncology
Background:
- Glutathione (GSH) is a key intracellular antioxidant.
- Overexpressed GSH in cancer cells reduces the effectiveness of photodynamic therapy (PDT) by scavenging reactive oxygen species (ROS).
Purpose of the Study:
- To develop a GSH-responsive ruthenium(II) complex for simultaneous GSH imaging and enhanced PDT.
- To evaluate the probe's efficacy in cancer cell imaging and phototoxicity.
Main Methods:
- Synthesis of a novel GSH-responsive Ru(II) complex, Ru(phen)2(bpy-nap)(PF6)2.
- Assessment of GSH-sensing capabilities, including phosphorescence response and detection limit.
- In vitro imaging of endogenous and exogenous GSH in HepG2 cells.
- Evaluation of ROS generation and phototoxicity under specific light irradiation.
- Mitochondrial localization studies.
Main Results:
- The Ru(II) complex demonstrated excellent GSH-sensing with a low detection limit (0.05 μM) and a significant phosphorescence turn-on response.
- Successful visualization of GSH in HepG2 cells.
- The probe exhibited high photostability, generated both Type I and Type II ROS, and showed potent phototoxicity against cancer cells.
- Selective localization within cancer cell mitochondria was observed.
Conclusions:
- Ru(phen)2(bpy-nap)(PF6)2 is a promising dual-functional phosphorescence probe for GSH detection.
- This probe enhances PDT efficacy by overcoming GSH-mediated ROS scavenging.
- The probe's mitochondrial targeting capability further boosts its therapeutic potential in cancer treatment.
