Theranostics 2016; 6(13):2458-2487. doi:10.7150/thno.16183 This issue


Beyond the Barriers of Light Penetration: Strategies, Perspectives and Possibilities for Photodynamic Therapy

Srivalleesha Mallidi1, Sriram Anbil1,2,3*, Anne-Laure Bulin1*, Girgis Obaid1*, Megumi Ichikawa1, Tayyaba Hasan1✉

1. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114;
2. Howard Hughes Medical Institute, Chevy Chase, MD, 20815;
3. The University of Texas School of Medicine at San Antonio, San Antonio, TX 78229.
*Authors contributed equally to the work.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
Mallidi S, Anbil S, Bulin AL, Obaid G, Ichikawa M, Hasan T. Beyond the Barriers of Light Penetration: Strategies, Perspectives and Possibilities for Photodynamic Therapy. Theranostics 2016; 6(13):2458-2487. doi:10.7150/thno.16183. Available from

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Graphic abstract

Photodynamic therapy (PDT) is a photochemistry based treatment modality that involves the generation of cytotoxic species through the interactions of a photosensitizer molecule with light irradiation of an appropriate wavelength. PDT is an approved therapeutic modality for several cancers globally and in several cases has proved to be effective where traditional treatments have failed. The key parameters that determine PDT efficacy are 1. the photosensitizer (nature of the molecules, selectivity, and macroscopic and microscopic localization etc.), 2. light application (wavelength, fluence, fluence rate, irradiation regimes etc.) and 3. the microenvironment (vascularity, hypoxic regions, stromal tissue density, molecular heterogeneity etc.). Over the years, several groups aimed to monitor and manipulate the components of these critical parameters to improve the effectiveness of PDT treatments. However, PDT is still misconstrued to be a surface treatment primarily due to the limited depths of light penetration. In this review, we present the recent advances, strategies and perspectives in PDT approaches, particularly in cancer treatment, that focus on increasing the 'damage zone' beyond the reach of light in the body. This is enabled by a spectrum of approaches that range from innovative photosensitizer excitation strategies, increased specificity of phototoxicity, and biomodulatory approaches that amplify the biotherapeutic effects induced by photodynamic action. Along with the increasing depth of understanding of the underlying physical, chemical and physiological mechanisms, it is anticipated that with the convergence of these strategies, the clinical utility of PDT will be expanded to a powerful modality in the armamentarium for the management of cancer.

Keywords: photodynamic therapy, light penetration