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

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.

Administration of particulate oxygen generators improves skeletal muscle contractile function after ischemia-reperfusion injury in the rat hindlimb.

Extended tourniquet application, often associated with battlefield extremity trauma, can lead to severe ischemia-reperfusion (I/R) injury in skeletal muscle. Particulate oxygen generators (POGs) can be directly injected into tissue to supply oxygen to attenuate the effects of I/R injury in muscle. The goal of this study was to investigate the efficacy of a sodium percarbonate (SPO)-based POG formulation in reducing ischemic damage in a rat hindlimb during tourniquet application. Male Lewis rats were anesthetized and underwent tourniquet application for 3 h at a pressure of 300 mmHg. Shortly after tourniquet inflation, animals received intramuscular injections of either 0.2 mg/mL SPO with catalase (n = 6) or 2.0 mg/mL SPO with catalase (n = 6) directly into the tibialis anterior (TA) muscle. An additional Tourniquet-Only group (n = 12) received no intervention. Functional recovery was monitored by in vivo contractile testing of the hindlimb at 1, 2, and 4 wk after injury. By the 4 wk time point, the Low-Dose POG group continued to show improved functional recovery (85% of baseline) compared with the Tourniquet-Only (48%) and High-Dose POG (56%) groups. In short, the low-dose POG formulation appeared, at least in part, to mitigate the impact of ischemic tissue injury, thus improving contractile function after tourniquet application. Functional improvement correlated with maintenance of larger muscle fiber cross-sectional area and the presence of fewer fibers containing centrally located nuclei. As such, POGs represent a potentially attractive therapeutic solution for addressing I/R injuries associated with extremity trauma.NEW & NOTEWORTHY Skeletal muscle contraction was evaluated in the same animals at multiple time points up to 4 wk after injury, following administration of particulate oxygen generators (POGs) in a clinically relevant rat hindlimb model of tourniquet-induced ischemia. The observed POG-mediated improvement of muscle function over time confirms and extends previous studies to further document the potential clinical applications of POGs. Of particular significance in austere environments, this technology can be applied in the absence of an intact circulation.

Assessment of Nanoparticle-Mediated Tumor Oxygen Modulation by Photoacoustic Imaging.

Photoacoustic imaging (PAI) is an invaluable tool in biomedical imaging, as it provides anatomical and functional information in real time. Its ability to image at clinically relevant depths with high spatial resolution using endogenous tissues as contrast agents constitutes its major advantage. One of the most important applications of PAI is to quantify tissue oxygen saturation by measuring the differential absorption characteristics of oxy and deoxy Hb. Consequently, PAI can be utilized to monitor tumor-related hypoxia, which is a crucial factor in tumor microenvironments that has a strong influence on tumor invasiveness. Reactive oxygen species (ROS)-based therapies, such as photodynamic therapy, radiotherapy, and sonodynamic therapy, are oxygen-consuming, and tumor hypoxia is detrimental to their efficacy. Therefore, a persistent demand exists for agents that can supply oxygen to tumors for better ROS-based therapeutic outcomes. Among the various strategies, NP-mediated supplemental tumor oxygenation is especially encouraging due to its physio-chemical, tumor targeting, and theranostic properties. Here, we focus on NP-based tumor oxygenation, which includes NP as oxygen carriers and oxygen-generating strategies to alleviate hypoxia monitored by PAI. The information obtained from quantitative tumor oxygenation by PAI not only supports optimal therapeutic design but also serves as a highly effective tool to predict therapeutic outcomes.