Next Article in Journal
The Influence of Genetic Polymorphisms and Psychosocial Determinants on Suicidal Behaviors: A Case–Control Study of CRHR1, NTRK2, and FKBP5
Previous Article in Journal
Exploring the Protective Effects of Taxifolin in Cardiovascular Health: A Comprehensive Review
Previous Article in Special Issue
Patient Stratification for Serum LDH Levels Reveals Distinct CLA+ T-Cell Cytokine Secretion in Response to HDM, Clinical Features and Allergic Comorbidities
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Review

Optimization of Photodynamic Therapy in Dermatology: The Role of Light Fractionation

by
Luis Alonso-Mtz de Salinas
*,
Emilio Garcia-Mouronte
,
Jorge Naharro-Rodriguez
,
Luis Alfonso Perez-Gonzalez
and
Montserrat Fernández-Guarino
*
Dermatology Department, Hospital Universitario Ramon y Cajal, Carretera M-607 km 9.1, 28034 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(16), 8054; https://doi.org/10.3390/ijms26168054 (registering DOI)
Submission received: 18 June 2025 / Revised: 18 August 2025 / Accepted: 19 August 2025 / Published: 20 August 2025
(This article belongs to the Special Issue Dermatology: Advances in Pathophysiology and Therapies (2nd Edition))

Abstract

Photodynamic therapy (PDT) has become a widely used modality for treating actinic keratosis (AK) and non-melanoma skin cancers (NMSC), as well as other inflammatory or infectious diseases. Despite its efficacy, limitations such as incomplete responses and pain have motivated the exploration of protocol enhancements. This review examines the clinical and biological rationale for light fractionation—dividing the total light dose into two separate exposures with a dark interval—as a strategy to improve PDT outcomes. We reviewed preclinical and clinical studies evaluating fractionated illumination using 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL). The findings consistently demonstrate superior efficacy of fractionated schemes, particularly with ALA, showing higher complete response rates in AK, superficial basal cell carcinoma (sBCC), and Bowen’s disease (BD), and improved long-term tumor control compared to single illumination. The better outcomes are attributed to increased reactive oxygen species (ROS) generation following tissue reoxygenation during the dark interval and greater susceptibility of partially damaged cells to subsequent illumination. Fractionated PDT also shows a favorable safety and cosmetic profile. These results support considering light fractionation protocols as a standard approach for optimizing PDT efficacy in dermatologic oncology, particularly in lesions with limited depth and high recurrence risk.
Keywords: photodynamic therapy; light fractionation; actinic keratosis; basal cell carcinoma; 5-aminolevulinic acid; methyl aminolevulinate; reactive oxygen species; non-melanoma skin cancer photodynamic therapy; light fractionation; actinic keratosis; basal cell carcinoma; 5-aminolevulinic acid; methyl aminolevulinate; reactive oxygen species; non-melanoma skin cancer

Share and Cite

MDPI and ACS Style

Alonso-Mtz de Salinas, L.; Garcia-Mouronte, E.; Naharro-Rodriguez, J.; Perez-Gonzalez, L.A.; Fernández-Guarino, M. Optimization of Photodynamic Therapy in Dermatology: The Role of Light Fractionation. Int. J. Mol. Sci. 2025, 26, 8054. https://doi.org/10.3390/ijms26168054

AMA Style

Alonso-Mtz de Salinas L, Garcia-Mouronte E, Naharro-Rodriguez J, Perez-Gonzalez LA, Fernández-Guarino M. Optimization of Photodynamic Therapy in Dermatology: The Role of Light Fractionation. International Journal of Molecular Sciences. 2025; 26(16):8054. https://doi.org/10.3390/ijms26168054

Chicago/Turabian Style

Alonso-Mtz de Salinas, Luis, Emilio Garcia-Mouronte, Jorge Naharro-Rodriguez, Luis Alfonso Perez-Gonzalez, and Montserrat Fernández-Guarino. 2025. "Optimization of Photodynamic Therapy in Dermatology: The Role of Light Fractionation" International Journal of Molecular Sciences 26, no. 16: 8054. https://doi.org/10.3390/ijms26168054

APA Style

Alonso-Mtz de Salinas, L., Garcia-Mouronte, E., Naharro-Rodriguez, J., Perez-Gonzalez, L. A., & Fernández-Guarino, M. (2025). Optimization of Photodynamic Therapy in Dermatology: The Role of Light Fractionation. International Journal of Molecular Sciences, 26(16), 8054. https://doi.org/10.3390/ijms26168054

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop