AUTHOR=Gamal-Eldeen Amira M. , Alrehaili Amani A. , Alharthi Afaf , Raafat Bassem M. 

TITLE=Effect of Combined Perftoran and Indocyanine Green-Photodynamic Therapy on HypoxamiRs and OncomiRs in Lung Cancer Cells

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.844104

DOI=10.3389/fphar.2022.844104

ISSN=1663-9812

ABSTRACT=<p>Indocyanine green (ICG) is a nontoxic registered photosensitizer used as a diagnostic tool and for photodynamic therapy (PDT). Hypoxia is one the main factors affecting PDT efficacy. Perfluorodecalin emulsion (Perftoran<sup>®</sup>) is a known oxygen carrier<bold>.</bold> This study investigated the effect of Perftoran<sup>®</sup> on ICG/PDT efficacy in presence and absence of Perftoran<sup>®</sup><italic>via</italic> evaluation of phototoxicity by MTT; hypoxia estimation by pimonidazole, HIF-1<italic>α</italic>/<italic>β</italic> by ELISA, and 17 miRNAs (tumor suppressors, oncomiRs, and hypoxamiRs) were analyzed by qPCR. Compared to ICG/PDT, Perftoran<sup>®</sup>/ICG/PDT led to higher photocytotoxicity, inhibited pimonidazole hypoxia adducts, inhibited HIF-1<italic>α</italic>/<italic>β</italic> concentrations, induced the expression of tumor-suppressing miRNAs let-7b/d/f/g, and strongly inhibited the pro-hypoxia miRNA let-7i. Additionally, Perftoran<sup>®</sup>/ICG/PDT suppressed the expression of the oncomiRs miR-155, miR-30c, and miR-181a and the hypoxamiRs miR-210 and miR-21 compared to ICG/PDT. In conclusion, Perftoran<sup>®</sup> induced the phototoxicity of ICG/PDT and inhibited ICG/PDT-hypoxia <italic>via</italic> suppressing HIF-<italic>α</italic>/<italic>β</italic>, miR-210, miR-21, let-7i, miR-15a, miR-30c, and miR-181a and by inducing the expression of let-7d/f and miR-15b.</p>