Multiple Functions Integrated inside a Single Molecule for Amplification of Photodynamic Therapy Activity
Xianqing Shi1, Qichen Zhan1, Yanqing Li1
1College of Chemistry and Materials Science, Jiangsu Key Laboratory of Biofunctional Materials, Jiangsu Collaborative Innovation Centre of Biomedical Functional Materials, Key Laboratory of Applied Photochemistry , Nanjing Normal University , Nanjing , Jiangsu 210023 , China.
Molecular Pharmaceutics
|December 6, 2019
Summary
This study introduces a novel photosensitizer (Arg-ZnPc) that releases nitric oxide (NO) to enhance photodynamic therapy (PDT). This strategy improves cancer treatment by ensuring efficient peroxynitrite anion formation and leveraging NO
Area of Science:
- Photodynamic Therapy
- Cancer Treatment
- Nitric Oxide Biology
Background:
- Nitric oxide (NO) exhibits dual roles in photodynamic therapy (PDT), influencing prosurvival and prodeath outcomes.
- The efficiency of peroxynitrite anion (ONOO-) generation, crucial for PDT efficacy, depends on the proximity of nitric oxide (NO) and superoxide anion (O2•-) sources.
- Optimizing NO and O2•- co-localization is key to enhancing PDT effectiveness.
Purpose of the Study:
- To design and synthesize a novel photosensitizer (PS) capable of acting as both a PS and a nitric oxide (NO) donor.
- To investigate a strategy for localized and simultaneous generation of NO and reactive oxygen species (ROS) to promote peroxynitrite anion (ONOO-) formation.
- To evaluate the synergistic effects of enhanced ONOO- generation and NO's multifaceted roles in improving cancer treatment outcomes via PDT.
Main Methods:
- Synthesis of l-arginine (Arg) ethyl ester-modified zinc phthalocyanine (Arg-ZnPc) as a dual-function photosensitizer and NO donor.
- Irradiation of Arg-ZnPc to induce reactive oxygen species (ROS) generation, leading to the oxidation of guanido moieties and subsequent NO release.
- In vitro and in vivo experiments to assess the efficacy of Arg-ZnPc in enhancing PDT through ONOO- formation and NO-mediated synergistic effects.
Main Results:
- The designed Arg-ZnPc successfully released NO upon light irradiation, driven by ROS-mediated oxidation.
- The strategy ensured localized and simultaneous generation of O2•- and NO, facilitating efficient ONOO- formation.
- Arg-ZnPc demonstrated enhanced PDT activity in vitro and in vivo, attributed to effective ONOO- generation and NO's synergistic anticancer functions.
Conclusions:
- The developed Arg-ZnPc effectively functions as a photosensitizer and nitric oxide (NO) donor, enabling localized ONOO- generation.
- NO's synergistic roles, including vasodilation, P-glycoprotein downregulation, and glutathione depletion, significantly contribute to enhanced cancer treatment.
- This approach represents a promising strategy for improving photodynamic therapy efficacy in cancer treatment.
