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Updated: Sep 3, 2025
Imaging Approaches to Assessments of Toxicological Oxidative Stress Using Genetically-encoded Fluorogenic Sensors
Published on: February 7, 2018
A photoactivatable theranostic probe for simultaneous oxidative stress-triggered multi-color cellular imaging and
Xiaohui Chen1, Zicong Zhang2, Wenshuai Luo3
1Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518060, China; Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China.
Abstract:
Simultaneous in situ monitoring critical organelles upon oxidative stress and implementing therapeutics utilizing oxidative stress are of vital importance and remain challenging task. Herein, we rationally design and facilely synthesized a photoactivatable fluorescent probe bearing 1,4-dihydropyridine moiety with aggregation-induced emission (AIE) tendency, namely TPA-DHPy, which can rapidly transform into its pyridine counterpart TPA-Py via photo-oxidative dehydrogenation showing strong polarity sensitivity and largely red-shifted emission. TPA-DHPy- and TPA-Py-based type I/type II photosensitization is able to effectively generate reactive oxygen species to induce in situ oxidative stress under white light irradiation. TPA-DHPy can be taken up by cancer cells, and gradually light up lipid droplets (LDs) and endoplasmic reticulum (ER) during photoactivatable process, as well as in situ monitoring difference and alteration of their microenvironment upon oxidative stress by means of multi-color fluorescence imaging in lambda mode. Furthermore, the in situ generated TPA-Py is capable of further destroying the functions of LDs and ER with prolonging the irradiation time, and remarkably inhibiting tumor growth under white light irradiation by the way of photodynamic therapy. This study thus offers useful insights into designing a new generation of theranostic agents towards imaging-guided precise cancer therapy.
Insights
Researchers developed a novel photoactivatable fluorescent probe for real-time monitoring of oxidative stress in cancer cells. This probe enables simultaneous imaging and photodynamic therapy, effectively inhibiting tumor growth.
Area of Science:
- Biomedical Engineering
- Chemical Biology
- Cancer Research
Background:
- Simultaneous in situ monitoring of organelles during oxidative stress and therapeutic interventions remain challenging.
- Developing agents that can both image and treat oxidative stress-induced cellular damage is crucial for cancer therapy.
Purpose of the Study:
- To design and synthesize a photoactivatable fluorescent probe (TPA-DHPy) for in situ monitoring of oxidative stress and subsequent photodynamic therapy.
- To investigate the probe's ability to track changes in lipid droplets (LDs) and endoplasmic reticulum (ER) microenvironments.
- To evaluate the therapeutic efficacy of the probe in inhibiting cancer cell growth.
Main Methods:
- Synthesis of a photoactivatable fluorescent probe (TPA-DHPy) with aggregation-induced emission (AIE) properties.
- Utilizing the probe for multi-color fluorescence imaging in lambda mode to monitor cellular microenvironments.
- Employing type I/type II photosensitization for reactive oxygen species generation and photodynamic therapy under white light irradiation.
Main Results:
- The probe TPA-DHPy transforms into TPA-Py, exhibiting polarity sensitivity and red-shifted emission, enabling sensitive imaging.
- Successful in situ monitoring of lipid droplets (LDs) and endoplasmic reticulum (ER) alterations under oxidative stress.
- Demonstrated effective photodynamic therapy by TPA-Py, leading to the destruction of LDs and ER functions and significant tumor growth inhibition.
Conclusions:
- The developed theranostic agent offers a novel approach for imaging-guided precise cancer therapy.
- The probe facilitates simultaneous monitoring and treatment of oxidative stress-related cellular damage.
- This study provides insights for designing next-generation theranostic agents for cancer treatment.
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