Low dose photodynamic therapy harmonizes with radiation therapy to induce beneficial effects on pancreatic heterocellular spheroids
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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
Anne-Laure Bulin, email: firstname.lastname@example.org
Tayyaba Hasan, email: email@example.com
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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