Photodynamic Therapy Applications in Oncology and Cancer Treatment

Photodynamic therapy (PDT) harnesses the interaction between a light‐activated photosensitiser, an appropriate wavelength of light and molecular oxygen to generate cytotoxic species that selectively destroy malignant cells and associated vasculature. Initially approved over three decades ago, PDT has evolved from surface‐level treatments to multimodal strategies that address deep‐seated tumours through advances in photosensitiser chemistry, light delivery and nanotechnology. Clinical applications now span dermatological malignancies, head and neck cancers, oesophageal and lung tumours, with emerging roles in intraoperative guidance and immunomodulation. Crucial improvements in tumour targeting, such as antibody fragments or peptide conjugates, have enhanced accumulation at disease sites while minimising off‐target effects. Integration with imaging modalities and concurrent photothermal therapy has expanded the utility of PDT, enabling real‐time monitoring of treatment efficacy and synergistic destruction of resistant cancer cells. Despite these gains, challenges remain in overcoming hypoxic microenvironments, limited light penetration and variable photosensitiser pharmacokinetics. Ongoing research addresses these hurdles by developing oxygen‐enhancing strategies, upconversion nanomaterials for deeper light activation and stimuli‐responsive delivery vehicles that trigger on‐demand release of therapeutic payloads. As a minimally invasive, immunogenic and repeatable modality, PDT holds growing promise in combination regimens with chemotherapy, radiotherapy and immunotherapy to achieve durable tumour control.

Research from Nature Portfolio

Recent studies have demonstrated the design of a self‐reporting nanobody conjugate that significantly improves photosensitiser retention in large‐volume tumour models. By site‐specific conjugation of a type I photosensitiser to a tumour‐targeting nanobody, the construct remains at the tumour site for extended periods and releases active agents upon light‐induced reactive oxygen species cleavage. The fluorescence recovery from the conjugate provides real‐time feedback on the occurrence and extent of photodynamic action. In preclinical models, a single administration followed by multiple light exposures achieved potent tumour suppression with high biosafety, exemplifying a paradigm for precise, long‐term retention and monitoring of photodynamic agents in oncology.

Photodynamic Therapy Applications in Oncology and Cancer Treatment publication trend

The graph below shows the total number of articles in photodynamic therapy applications in oncology and cancer treatment across all publications each year (not limited to Nature Index journals).

Technical terms

Photosensitiser: A molecule activated by light to transfer energy to oxygen, generating cytotoxic species.

Reactive oxygen species (ROS): Short‐lived, highly reactive oxygen‐containing molecules that induce cellular damage.

Upconversion nanoparticles: Nanomaterials that absorb near‐infrared light and emit visible wavelengths to activate photosensitisers in deep tissues.

Photothermal therapy (PTT): Treatment modality utilising light‐induced heat to ablate cancer cells, often combined with PDT for synergistic effects.

Self-reporting conjugate: A delivery system that emits a detectable signal upon photosensitiser activation, enabling real-time monitoring of treatment.

References

1. Self-reporting photodynamic nanobody conjugate for precise and sustainable large-volume tumor treatment. Nature Communications (2024).
2. pH-Responsive Upconversion Mesoporous Silica Nanospheres for Combined Multimodal Diagnostic Imaging and Targeted Photodynamic and Photothermal Cancer Therapy. ACS Nano (2023).
3. Photodynamic Therapy—Current Limitations and Novel Approaches. Frontiers in Chemistry (2021).
4. Oncologic Photodynamic Therapy: Basic Principles, Current Clinical Status and Future Directions. Cancers (2017).