Photodynamic Therapy Applications in Melanoma Treatment
Summary
Photodynamic therapy (PDT) harnesses light-activated photosensitisers to generate cytotoxic reactive oxygen species (ROS) and induce tumour cell death. In melanoma, the high melanin content and robust antioxidant defences have historically limited PDT efficacy. Recent advances address these challenges by developing novel photosensitiser chemistries, using prodrugs to exploit dysregulated haem biosynthesis, and integrating nanotechnology to improve solubility, bioavailability and selective delivery. Combination approaches—such as pairing PDT with immunomodulatory agents or metabolic sensitisers—are emerging to overcome intrinsic resistance and to engage anti-tumour immunity. Moreover, three-dimensional (3D) tumour models have refined preclinical assessment, revealing how tissue architecture and microvascular access influence light penetration and ROS generation. Globally, these innovations hold promise for minimally invasive management of primary and metastatic melanoma, offering targeted eradication with reduced systemic toxicity and the potential to synergise with existing surgical and systemic therapies.
Research from Nature Portfolio
Innovative work has demonstrated that flavin mononucleotide (FMN), a water-soluble derivative of vitamin B2, selectively accumulates in melanoma cells and upon blue-light irradiation induces apoptosis via on-site ROS generation. In vitro studies confirmed FMN uptake in diverse melanoma cell lines with minimal dark toxicity in non-malignant keratinocytes and fibroblasts. Real-time electrochemical monitoring of single cells validated ROS production under light exposure, while in vivo melanoma xenograft models showed tumour regression of 85–90 % over seven weeks following systemic FMN administration and targeted light delivery. This study underscores the potential of endogenous cofactor-derived photosensitisers for safe, efficient PDT in pigmented tumours.
Photodynamic Therapy Applications in Melanoma Treatment publication trend
The graph below shows the total number of articles in photodynamic therapy applications in melanoma treatment across all publications each year (not limited to Nature Index journals).
Technical terms
Photosensitiser: A light-absorbing compound that transfers energy to oxygen to produce cytotoxic ROS under specific wavelengths.
Reactive oxygen species (ROS): Chemically reactive molecules containing oxygen that induce cellular damage and apoptosis.
Nanocarrier: A nanoscale delivery vehicle designed to improve pharmacokinetics and target specificity of therapeutic agents.
Prodrug: An inactive precursor that is metabolically converted into an active photosensitiser within tumour cells.
Melanin: A natural pigment in skin cells that absorbs light and acts as an antioxidant, often reducing PDT efficacy in pigmented tumours.
References
- Photodynamic therapy of melanoma by blue-light photoactivation of flavin mononucleotide. Scientific Reports (2019).
- Photosensitizers-Loaded Nanocarriers for Enhancement of Photodynamic Therapy in Melanoma Treatment. Pharmaceutics (2023).
- Enhanced Delivery of 5‑Aminolevulinic Acid by Lecithin Invasomes in 3D Melanoma Cancer Model. Molecular Pharmaceutics (2023).
- Impact of Aluminium phthalocyanine nanoconjugate on melanoma stem cells. Artificial Cells Nanomedicine and Biotechnology (2023).
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