Effect of oxygen generating nanozymes on indocyanine green and IR 820 mediated phototherapy against oral cancer

Abstract

The hypoxic environment within a solid tumor is a limitation to the effectiveness of photodynamic therapy. Here, we demonstrate the use of oxygen generating nanozymes (CeO2, Fe3O4, and MnO2) to improve the photodynamic effect. The optimized combination of process parameters for irradiation was obtained using the Box Behnken experimental design. Indocyanine green, IR 820, and their different combinations with oxygen generators were studied for their effect on oral carcinoma. Dynamic light scattering technique showed the average particle size of CeO2, MnO2, and Fe3O4 to be 211 ± 16, and 157 ± 28, 143 ± 19 nm with PDI of 0.23, 0.28 and 0.20 and a zeta potential of −2.6 ± 0.45, −2.4 ± 0.60 and −6.1 ± 0.23 mV, respectively. The formation of metal oxides was confirmed using UV–visible, FTIR, and X-ray photon spectroscopies. The amount of dissolved oxygen produced by CeO2, MnO2, and Fe3O4 in the presence of H2O2 within 2 min was 1.7 ± 0.15, 1.7 ± 0.16, and 1.4 ± 0.12 mg/l, respectively. Growth inhibition studies in the FaDu oral carcinoma spheroid model showed a significant (P < 0.05) increase in growth reduction from 81 ± 2.9 and 88 ± 2.1% to 97 ± 1.2 and 99 ± 1.0% for ICG and IR 820, respectively, after irradiation (808 nm laser, 1 W/cm2, 5 min) in the presence of CeO2 (25 μg/ml). In conclusion, oxygen-generating nanozymes can improve the photodynamic effect of ICG and IR 820.