Research Papers:

Low dose photodynamic therapy harmonizes with radiation therapy to induce beneficial effects on pancreatic heterocellular spheroids

Anne-Laure Bulin _, Mans Broekgaarden, Diane Simeone and Tayyaba Hasan

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Oncotarget. 2019; 10:2625-2643. https://doi.org/10.18632/oncotarget.26780

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Anne-Laure Bulin1, Mans Broekgaarden1, Diane Simeone2,3,4 and Tayyaba Hasan1

1Wellman Center for Photomedicine, Department of Dermatology, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA

2Department of Surgery, NYU Langone Health, New York, NY, USA

3Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA

4Department of Pathology, NYU Langone Health, New York, NY, USA

Correspondence to:

Anne-Laure Bulin, email: anne-laure.bulin@esrf.fr

Tayyaba Hasan, email: thasan@mgh.harvard.edu

Keywords: low dose photodynamic therapy; radiation therapy; spheroids; pancreatic cancer

Received: November 16, 2018    Accepted: February 21, 2019    Published: April 05, 2019


Photodynamic therapy (PDT) has seen long standing interest as a therapy for resistant cancers, but the main Achilles’ heel for its successful clinical exploitation is the use of poorly penetrating visible light. This limitation could be overcome by using radioluminescent nanoparticles, which can be excited during radiation therapy (RT) with penetrating X-rays. When infused in tumors, X-ray activated-nanoscintillators act as internal light sources and excite nearby photosensitizers. Recent studies demonstrated that it is realistic to achieve low dose PDT with current nanoscintillators. However, as the origin of enhanced RT efficacy with nanoscintillators may have varying origins, we aimed to answer the basic question: Is a combination of low-dose PDT beneficial to the RT efficacy in clinically relevant models of cancer?

Pancreatic cancer (PanCa) remains a lethal disease for which RT is part of the palliative care and for which PDT demonstrated promising results in clinical trial. We thus evaluated the combination of low-dose PDT and RT delivered in absence of nanoscintillators on various heterocellular spheroid models that recapitulate the clinical heterogeneity of PanCa. Although therapeutic effects emerged at different timepoints in each model, the RT/PDT combination uniformly achieved favorable outcomes. With RT providing stunted tumor growth while PDT drove adjuvant apoptotic and necrotic cell death, the combination produced significantly smaller and less viable PanCa spheroids.

In conclusion, the beneficial RT/PDT treatment outcomes encourage the further development of nanoscinitillators for X-ray-activated PDT. Assessment of such combination treatments should encompass multiparametric and temporally-spaced assessment of treatment effects in preclinical cancer models.

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