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Updated: Nov 24, 2025
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Photogenerated Holes Mediated Nitric Oxide Production for Hypoxic Tumor Treatment
Xiao Fang1, Shuxian Cai1, Min Wang1
1MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, 350108, P. R. China.
Abstract:
Nitric oxide (NO) is a gaseous signal molecule with multiple physiological functions, and it also plays a key role in cancer therapy. However, the production of NO which depends on O2 or H2 O2 is limited within the tumor microenvironment, leading to unsatisfactory anticancer effect. Herein, we report a NO-based phototherapeutic strategy mediated by photogenerated holes for hypoxic tumors, which is achieved by irradiation of the poly-L-arginine modified carbon-dots-doped graphitic carbon nitride nanomaterial (ArgCCN). Upon red light irradiation, the photogenerated holes on ArgCCN oxidized water into H2 O2 which subsequently oxidized the arginine residues to produce NO. In vitro and in vivo experiments showed that the high concentration of NO produced by ArgCCN could induce cancer cell apoptosis. The presented phototherapeutic strategy is based on microenvironment-independent photogenerated holes mediated oxidation reaction, paving the way for the development of NO therapeutic strategy.
Insights
This study introduces a novel phototherapy for hypoxic tumors using modified carbon dots (ArgCCN) that generate nitric oxide (NO) independently of oxygen. This approach effectively induces cancer cell apoptosis, offering a promising new cancer treatment strategy.
Area of Science:
- Biomedical Engineering
- Materials Science
- Oncology
Background:
- Nitric oxide (NO) is crucial for physiological functions and cancer therapy.
- Limited oxygen and hydrogen peroxide in tumors restrict NO production, hindering current NO-based cancer treatments.
- Developing oxygen-independent NO generation strategies is vital for effective cancer therapy.
Purpose of the Study:
- To develop a novel phototherapeutic strategy for hypoxic tumors using a microenvironment-independent NO generation system.
- To investigate the efficacy of poly-L-arginine modified carbon-dots-doped graphitic carbon nitride nanomaterial (ArgCCN) for NO-based cancer treatment.
- To explore the potential of photogenerated holes in driving NO production for therapeutic applications.
Main Methods:
- Synthesis of poly-L-arginine modified carbon-dots-doped graphitic carbon nitride nanomaterial (ArgCCN).
- Red light irradiation of ArgCCN to generate photogenerated holes.
- Oxidation of water by photogenerated holes to produce hydrogen peroxide (H2O2).
- Oxidation of arginine residues by H2O2 to generate nitric oxide (NO).
- In vitro and in vivo experiments to evaluate cancer cell apoptosis induction.
Main Results:
- ArgCCN efficiently produced NO upon red light irradiation via a photogenerated hole-mediated pathway.
- The NO production mechanism was independent of the tumor microenvironment's oxygen or H2O2 levels.
- High concentrations of NO induced significant cancer cell apoptosis in vitro and in vivo.
- The phototherapeutic strategy demonstrated effective tumor suppression.
Conclusions:
- The developed ArgCCN nanomaterial offers a novel phototherapeutic strategy for hypoxic tumors by generating NO independently of the tumor microenvironment.
- This microenvironment-independent, photogenerated hole-mediated oxidation reaction provides a new avenue for NO-based cancer therapy.
- The findings pave the way for developing advanced NO therapeutic strategies for challenging tumor conditions.
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