Boosting Hydroxyl Radical Generation with Nitrogen Vacancy-Modified Carbon Nitride for Triggering Dual Damage of Cancer Nucleus DNA-Mitochondria against Hypoxic Tumors

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 (N_V-PCN), a novel metal-free and O₂-independent Photosensitizer designed for PDT. N_V-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 N_V 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, N_V-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, N_V-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.

DNA-damage repair; hydroxyl radical; nitrogen vacancy; photodynamic therapy; polymeric carbon nitride.