Activatable Dual ROS-Producing Probe for Dual Organelle-Engaged Photodynamic Therapy
Jian Li1, Tingting Wang2, Feng Jiang1
1State Key Laboratory for Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, the Key Laboratory for Chemical Biology of Fujian Province, The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, and Innovation Center for Cell Signaling Network, Xiamen University, Xiamen 361005, China.
Abstract:
Photodynamic therapy (PDT) necessitates approaches capable of increasing antitumor effects while decreasing nonspecific photodamage. We herein report an activatable probe (Glu-PyEB) comprising two distinct photosensitizers with mutually suppressed photodynamics. Activation by tumor-associated γ-glutamyltranspeptidase gives rise to a generator of superoxide radical (O2-•) accumulated in lysosomes and a producer of singlet oxygen (1O2) enriched in mitochondria. This enables light-irradiation-triggered damage of lysosomes and mitochondria, robust cell death, and tumor retardation in vivo, showing the use of paired photosensitizers subjected to reciprocally suppressed photodynamics for activatable PDT.
Insights
This study introduces an activatable probe for photodynamic therapy (PDT) that enhances antitumor effects. The probe uses paired photosensitizers to target cancer cells, reducing damage to healthy tissues.
Area of Science:
- Biomedical Engineering
- Photochemistry
- Cancer Therapy
Background:
- Photodynamic therapy (PDT) faces challenges in maximizing antitumor efficacy while minimizing off-target photodamage.
- Developing targeted and activatable therapeutic agents is crucial for improving PDT outcomes.
Purpose of the Study:
- To design and evaluate an activatable probe (Glu-PyEB) for enhanced photodynamic therapy.
- To investigate a novel approach using paired photosensitizers with suppressed photodynamics for targeted cancer treatment.
Main Methods:
- Synthesis of an activatable probe (Glu-PyEB) incorporating two distinct photosensitizers.
- Investigating the probe's activation by tumor-associated γ-glutamyltranspeptidase.
- Assessing the generation of superoxide radicals in lysosomes and singlet oxygen in mitochondria upon activation and light irradiation.
- Evaluating the probe's efficacy in inducing cell death and inhibiting tumor growth in vivo.
Main Results:
- The activatable probe (Glu-PyEB) demonstrated mutually suppressed photodynamics until activated by γ-glutamyltranspeptidase.
- Activated probe led to targeted generation of superoxide radicals in lysosomes and singlet oxygen in mitochondria.
- Light irradiation triggered lysosomal and mitochondrial damage, resulting in robust cancer cell death.
- Significant tumor retardation was observed in vivo, confirming the probe's therapeutic potential.
Conclusions:
- The developed activatable probe (Glu-PyEB) offers a promising strategy for enhancing photodynamic therapy.
- The use of paired photosensitizers with reciprocally suppressed photodynamics enables targeted activation and improved antitumor effects.
- This approach effectively reduces nonspecific photodamage, paving the way for safer and more effective cancer treatments.
