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

Amira M Gamal-Eldeen; Amani A Alrehaili; Afaf Alharthi; Bassem M Raafat

doi:10.3389/fphar.2022.844104

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

Front Pharmacol. 2022 Mar 16:13:844104. doi: 10.3389/fphar.2022.844104. eCollection 2022.

Authors

Amira M Gamal-Eldeen¹, Amani A Alrehaili¹, Afaf Alharthi¹, Bassem M Raafat²

Affiliations

¹ Clinical Laboratory Sciences Department, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia.
² Radiological Sciences Department, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia.

Abstract

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^®) is a known oxygen carrier. This study investigated the effect of Perftoran^® on ICG/PDT efficacy in presence and absence of Perftoran^® via evaluation of phototoxicity by MTT; hypoxia estimation by pimonidazole, HIF-1α/β by ELISA, and 17 miRNAs (tumor suppressors, oncomiRs, and hypoxamiRs) were analyzed by qPCR. Compared to ICG/PDT, Perftoran^®/ICG/PDT led to higher photocytotoxicity, inhibited pimonidazole hypoxia adducts, inhibited HIF-1α/β concentrations, induced the expression of tumor-suppressing miRNAs let-7b/d/f/g, and strongly inhibited the pro-hypoxia miRNA let-7i. Additionally, Perftoran^®/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^® induced the phototoxicity of ICG/PDT and inhibited ICG/PDT-hypoxia via suppressing HIF-α/β, 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.

Keywords: ICG = indocyanine green; PDT—photodynamic therapy; Perftoran; hypoxamiRs; hypoxia; lung cancer; oncomirs.