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Updated: Jan 7, 2026
Imaging Approaches to Assessments of Toxicological Oxidative Stress Using Genetically-encoded Fluorogenic Sensors
Published on: February 7, 2018
Genetic approaches for targeted oxidative stress
Aninda Dey1,2, Ryan P Barnes1,2
1Department of Cancer Biology, The University of Kansas Medical Center, Kansas City, Kansas, 66160, United States.
Abstract:
Cancer cells display dysregulated metabolic programs, which result in excessive reactive oxygen species (ROS) leading to oxidative stress. ROS reaction with macromolecules, including proteins, lipids, and nucleic acids, can result in damaging modifications with alter or nullify function. While tumors upregulate antioxidant defences for viability, they remain sensitive to additional oxidant perturbations. Because of this, therapies that overwhelm cancers with ROS are gaining clinical attention due to their potential targeting of diseased tissue over normal tissue. In this review, we summarize the available genetic tools for targeted ROS production in both cellular and organismal models, specifically focusing on tools with spatial and temporal control. Largely, these approaches use light to activate a chromophore in the cell, which produces ROS for protein inactivation, DNA damage, or cell ablation. These photosensitizers are genetically fused to target proteins of interest, and all have advantages and disadvantages for both basic and translational research, which we discuss below.
Insights
Cancer therapies using genetically engineered tools to produce reactive oxygen species (ROS) show promise. These light-activated photosensitizers target cancer cells, offering new avenues for oxidative stress-based treatments.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Cancer cells exhibit altered metabolism, leading to excessive reactive oxygen species (ROS) and oxidative stress.
- Tumors possess upregulated antioxidant defenses but remain vulnerable to further oxidative damage.
- ROS can modify proteins, lipids, and nucleic acids, impairing cellular function.
Purpose of the Study:
- To review genetic tools for targeted ROS production in cellular and organismal models.
- To focus on tools offering spatial and temporal control over ROS generation.
- To discuss the advantages and disadvantages of these tools for research and clinical applications.
Main Methods:
- Genetic fusion of photosensitizers to target proteins.
- Light-induced activation of photosensitizers to generate ROS.
- Application in cellular and organismal models for studying ROS effects.
Main Results:
- Development of genetically encoded tools for controlled ROS production.
- Demonstration of ROS-induced protein inactivation, DNA damage, and cell ablation.
- Evaluation of photosensitizer efficacy and specificity in different models.
Conclusions:
- Genetically targeted ROS production offers a promising strategy for cancer therapy.
- Photosensitizer-based approaches provide spatial and temporal control over oxidative stress.
- These tools have significant potential for both basic research and translational applications in oncology.
