Graphene Oxide Nanosheets as Direct Photosensitizers for Photodynamic Therapy in a Size‐Dependent Manner

Why It Matters

Large‑size GO offers a scalable, low‑toxicity photosensitizer that overcomes stability and solubility limits of conventional PDT agents, opening new avenues for effective cancer treatment.

Key Takeaways

• Larger GO (~3.5 µm) generates more ROS under NIR
• Small GO shows minimal photodynamic effect
• Large GO reduces cell viability to 8% after irradiation
• Single NIR dose with large GO ablates tumors in mice
• GO remains low toxicity without light, even under hypoxia

Pulse Analysis

Photodynamic therapy (PDT) has long been hampered by photosensitizers that degrade quickly, dissolve poorly, or cause off‑target toxicity. Graphene oxide, traditionally valued for its drug‑delivery capabilities, now emerges as a carrier‑free photosensitizer when engineered at a sufficient lateral dimension. The size‑dependent phenomenon stems from larger GO sheets providing broader light‑absorption cross‑sections and facilitating more efficient energy transfer to molecular oxygen, thereby producing reactive oxygen species (ROS) upon near‑infrared (NIR) illumination. This discovery bridges nanomaterial science with clinical oncology, offering a more stable and biocompatible alternative to organic dyes.

In vitro experiments reveal that GO sheets around 3,500 nm exhibit negligible cytotoxicity at 200 µg/mL without light, yet under NIR exposure they slash HSC‑3 oral carcinoma cell viability to just 8%. Importantly, the ROS surge persists even under hypoxic conditions, a common obstacle in solid‑tumor environments that limits many PDT agents. The pronounced size effect underscores the necessity of precise nanofabrication: smaller GO fragments fail to generate sufficient ROS, highlighting a clear design rule for future nanophotonic therapeutics.

Translating these findings in vivo, a single intravenous dose of large GO followed by one NIR pulse achieved substantial tumor ablation in mice, eliminating the need for repeated dosing or adjunctive drugs. This streamlined protocol reduces treatment complexity and potential side effects, positioning size‑optimized GO as a promising candidate for clinical PDT pipelines. Future work will likely focus on scaling production, assessing long‑term biodistribution, and integrating GO‑based PDT with immunotherapy to exploit synergistic anti‑cancer mechanisms.