The efficacy of photodynamic therapy (PDT) strictly depends on the availability of molecular oxygen to trigger the light-induced generation of reactive species. Fluorocarbons have an increased ability to dissolve oxygen and are attractive tools for gas delivery. We synthesized three fluorous derivatives of chlorin with peripheral polyfluoroalkyl substituents. These compounds were used as precursors for preparing nanoemulsions with perfluorodecalin as an oxygen depot. Therefore, our formulations contained hydrophobic photosensitizers capable of absorbing monochromatic light in the long wavelength region and the oxygen carrier. These modifications did not alter the photosensitizing characteristics of chlorin such as the generation of singlet oxygen, the major cytocidal species in PDT. Emulsions readily entered HCT116 colon carcinoma cells and accumulated largely in mitochondria. Illumination of cells loaded with emulsions rapidly caused peroxidation of lipids and the loss of the plasma membrane integrity (photonecrosis). Most importantly, in PDT settings, emulsions potently sensitized cells cultured under prolonged (8 weeks) hypoxia as well as cells after oxygen depletion with sodium sulfite (acute hypoxia). The photodamaging potency of emulsions in hypoxia was significantly more pronounced compared to emulsion-free counterparts. Considering a negligible dark cytotoxicity, our materials emerge as efficient and biocompatible instruments for PDT-assisted eradication of hypoxic cells.
The cause of acute and severe hypoxia of the organism is acute posthemorrhagic anemia. To eliminate posthemorrhagic anemia in animals, the perfluorocarbon blood substitute Perftoran (Russia) with a gas-transporting function was used. The aim of this study was to determine the clinical effectiveness of the perfluorocarbon based blood substitute Perftoran with a gas-carrying function in acute posthemorrhagic anemia in animals and reveal possible side effect of the blood substitute and remove them. In the study conducted in the Clinic of Veterinary Medicine of Pushchino Research Center (Russia) participated 20 cats of both sexes, who were admitted with internal bleeding as a result of injuries. The animals were divided into two groups: the control and the treatment groups (10 per group). All animals with anemia were examined according to the standard scheme: anamnesis vitae and anamnesis morbi, physical examination (basic methods of research were used), additional methods that were used: complete blood count (CBC) and biochemical analysis of blood (BA), microscopy of blood smears, abdominal ultrasonography. Based on the obtained results, we can conclude that the use of the gas-carrying substitute for donor blood Perftoran in the treatment group of animals with posthemorrhagic anemia, which resulted from polytrauma, eliminated tissue hypoxia; the treatment of the animals in the control group with standard solutions (by infusing Stabisol) without gas transport correction led to the development of persistent hypoxia, which persisted to the stage of reticulocyte crisis.
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