Photodynamic therapy relieves colitis and prevents colitis-associated carcinogenesis in mice.

Inflamm Bowel Dis

*Université de Lorraine, Centre de recherche en automatique de Nancy, Vandoeuvre-lès-Nancy, France; †Centre national de la recherche scientifique, Centre de recherche en automatique de Nancy, UMR7039, Vandœuvre-lès-Nancy, France; ‡Institut de Cancérologie de Lorraine, Vandoeuvre-lès-Nancy, France; §Institut National de la Santé et de la Recherche Médicale, U954, Vandoeuvre-lès-Nancy, France; ‖Gènes Diffusion, Douai, France; ¶Pegase-Biosciences, Institut Pasteur de Lille, Lille, France; and **Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, UMR1019, Lille, France.

Published: May 2015

Background: Inflammatory bowel diseases are incurable illnesses of the gastrointestinal tract, which substantially enhance the risk of developing colorectal carcinogenesis. Conventional photodynamic therapy is a clinically approved therapeutic modality used in the treatment of neoplastic diseases. Recent preclinical and clinical studies have shown that photodynamic therapy with low doses of photosensitizer and/or light improves inflammatory conditions, including colitis. This study aims therefore at investigating the therapeutic potential of low-dose photodynamic therapy (LDPDT) with a liposomal formulation of meta-tetra(hydroxyphenyl)chlorin (namely Foslip) in the prevention of colitis-associated cancer in mice.

Methods: LDPDT efficacy was evaluated by endoscopic, macroscopic, and histological analysis. Myeloperoxidase levels were quantified by enzyme linked immunosorbent assay and cytokines expression by quantitative RT-PCR analysis. The integrity of the intestinal barrier was evaluated by immunostaining, and bacterial composition of the fecal microbiota was determined by 454 pyrosequencing of V3-V4 region of bacterial 16S rRNA genes.

Results: LDPDT reduced intestinal tumor growth by decreasing the expression of a wide range of inflammatory mediators and by lowering neutrophil influx. LDPDT treatment prevents onset of a dysbiotic microbiota in the colitis-associated cancer model.

Conclusions: LDPDT with Foslip could be considered as a novel treatment modality to prevent colorectal carcinogenesis in patients with inflammatory bowel disease.

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http://dx.doi.org/10.1097/MIB.0000000000000354DOI Listing

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