Stimulation and homogenization of the protoporphyrin IX endogenous production by photobiomodulation to increase the potency of photodynamic therapy

• Published in: Journal of photochemistry and photobiology. B, Biology Vol. 225; p. 112347
• Main Authors: Joniová, Jaroslava, Kazemiraad, Cyrus, Gerelli, Emmanuel, Wagnières, Georges
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 01.12.2021; Elsevier BV
• Subjects: Aminolevulinic acid; Animals; Cell death; Cell Line, Tumor; Cell survival; Chickens; Chorioallantoic membrane; Contrast agents; Fluorescence; Homogenization; Humans; Membrane potential; Membrane Potential, Mitochondrial; Membranes; Metabolism; Mitochondria; Optical Imaging; Photobiomodulation; Photochemotherapy; Photodynamic therapy; Photosensitizing Agents - therapeutic use; Protoporphyrin; Protoporphyrin IX; Protoporphyrins - biosynthesis; Reactive oxygen species; Reactive Oxygen Species - metabolism; Singlet oxygen; Stimulation; Tumors; Homogenization; Photodynamic therapy; Protoporphyrin IX; Photobiomodulation
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2021.112347

Protoporphyrin IX (PpIX) is produced in the mitochondria and used as fluorescent contrast agent or photosensitizer after exogenous 5-aminolevulinic acid (ALA) delivery in cancer photodynamic detection and therapy (PDT). Although routinely used in the clinics, the stimulated production of PpIX is often insufficient and/or heterogeneous within the lesions, thereby limiting the PDT performances. Since photobiomodulation, which is based on the illumination of the tissues with sub-thermal radiometric conditions in the red or near-infrared, is known to stimulate the cell metabolism, we have optimized these conditions in vitro. Some of them lead to the homogenization and strong stimulation of the PpIX endogenous production. Interestingly, combined sequentially, PBM enhanced significantly the potency of PpIX-based PDT in vitro and in vivo in tumors grown on the chicken embryo chorioallantoic membrane. These results are in excellent agreement with other assays based on measurements of the cell survival/death, the production of reactive oxygen species, including singlet oxygen, and the mitochondrial membrane potential. •Photobiomodulation increases endogenous protoporphyrin IX production.•Merge of photobiomodulation and photodynamic therapy leads to more efficient outcome.•Photobiomodulation homogenizes endogenous protoporphyrin IX production.