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Published on: March 17, 2023
Boosting Hydroxyl Radical Generation with Nitrogen Vacancy-Modified Carbon Nitride for Triggering Dual Damage of
Yuan Zhang1,2, Meixian Liu1,2, Shuyun Xue1,2
1Department of Oral and Maxillofacial Surgery, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People's Republic of China.
Introduction:
Oral squamous cell carcinoma (OSCC) is a prevalent and deadly cancer, with over 350,000 new cases yearly. A hypoxic tumor microenvironment is the bottleneck of photodynamic therapy (PDT) and significantly weakens overall therapeutic efficacy.
Methods:
In this study, we introduce nitrogen vacancy-modified PCN (NV-PCN), a novel metal-free and O2-independent photosensitizer designed for PDT. NV-PCN targets Cal-27-induced OSCC by reducing highly expressed H2O2 in tumors to highly reactive •OH. This innovative approach aims to overcome the limitations posed by the hypoxic environment and enhance the effectiveness of PDT in treating OSCC.
Results:
The introduction of NV not only further improves the cell accessibility of PCN by increasing the content of -NH2 but also provides more reactive sites for H2O2 reduction and facilitates carrier separation. Under illumination, NV-PCN generates a burst of •OH around the nuclei and mitochondria of Cal-27 cells, which effectively kills the cells via synchronously leading to DNA damage and mitochondrial dysfunction. Compared to the conventional photosensitizer chlorin e6, NV-PCN-based PDT exhibits excellent anticancer performance in vitro and in vivo, highlighting its potential as a next-generation therapeutic agent.
Conclusion:
Collectively, the high •OH-generation efficiency, strong anticancer activity, and overall safety of the O2-independent nanoparticle opens up new avenues for in-depth study on carbon nitride-based cancer PDT strategies. This work offers new hope for the effective treatment of OSCC and other challenging cancers.
Insights
This study introduces a novel oxygen-independent photosensitizer, NV-PCN, for photodynamic therapy (PDT) of oral squamous cell carcinoma (OSCC). NV-PCN effectively generates reactive hydroxyl radicals, overcoming tumor hypoxia and enhancing anticancer efficacy.
Area of Science:
- Biomedical Engineering
- Materials Science
- Oncology
Background:
- Oral squamous cell carcinoma (OSCC) presents a significant global health challenge, with over 350,000 new cases annually.
- Tumor hypoxia is a major limitation in photodynamic therapy (PDT), severely compromising treatment effectiveness.
Purpose of the Study:
- To develop a novel, oxygen-independent photosensitizer for enhanced PDT efficacy in OSCC.
- To investigate the mechanism of action and therapeutic potential of nitrogen vacancy-modified PCN (NV-PCN) in OSCC treatment.
Main Methods:
- Synthesis and characterization of nitrogen vacancy-modified PCN (NV-PCN), a metal-free photosensitizer.
- Evaluation of NV-PCN's ability to reduce hydrogen peroxide (H2O2) to hydroxyl radicals (•OH) in hypoxic conditions.
- Assessment of NV-PCN-based PDT efficacy in vitro (Cal-27 cells) and in vivo models of OSCC.
Main Results:
- NV-PCN demonstrated enhanced cell accessibility and increased reactive sites for H2O2 reduction.
- Illumination of NV-PCN induced significant •OH generation, leading to DNA damage and mitochondrial dysfunction in Cal-27 cells.
- NV-PCN-based PDT showed superior anticancer performance compared to conventional photosensitizers in vitro and in vivo.
Conclusions:
- NV-PCN is a promising oxygen-independent photosensitizer for PDT, effectively overcoming tumor hypoxia.
- The high •OH generation efficiency and anticancer activity of NV-PCN offer a new therapeutic strategy for OSCC.
- This study highlights the potential of carbon nitride-based nanoparticles in advancing cancer PDT.
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