Perfluorocarbon Nanoemulsions with Fluorous Chlorin-Type Photosensitizers for Antitumor Photodynamic Therapy in Hypoxia.

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.

Synthesis of 4-trifluoromethyl-2H-chromenes via the reaction of 2-(trifluoroacetyl)phenols with vinyltriphenylphosphonium chloride.

Substituted on the benzene ring 4-CF3-2H-chromenes have been prepared from substituted 2-(trifluoroacetyl)phenols and vinyltriphenylphosphonium chloride according to the Schweizer protocol in moderate to excellent yields. The influence of the type and the position of aromatic ring substituents on yields of 4-CF3-2H-chromenes have been investigated. It has been shown that 4-CF3-2H-chromenes are convenient precursors to 4-CF3-coumarins.

Novel Fluorinated Porphyrins Sensitize Tumor Cells to Photodamage in Normoxia and Hypoxia: Synthesis and Biocompatible Formulations.

BACKGROUND: Hypoxia renders tumor cells refractory to treatment. One way to overcome this problem is the design of drug delivery systems that contain the antitumor agent within an oxygen supply medium. OBJECTIVE: to evaluate whether the perfluorocarbon liquids (capable of retaining up to 50% v/v amounts of O2 gas) can be tools for delivery of photosensitizers to hypoxic tumors. METHOD: We synthesized a series of compounds in which fluoroaliphatic or fluoroaromatic moieties were conjugated to the porphyrin ring in meso-positions. Two derivatives were tested as the solutions prepared either from a dimethylformamide stock ('free' formulation) or from a perfluorocarbon emulsion in which the photosensitizer is entrapped in the oxygenated medium. RESULTS: In the emulsion the hydrophobic photosensitizer and the gas transporting liquid represented a biocompatible composition. Free formulations or perfluorocarbon emulsions of fluorinated porphyrins evoked little-to-null dark cytotoxicity. In contrast, each formulation triggered cell death upon light activation. Photodamage in the presence of fluorinated porphyrins was achievable not only at normoxic (20.9% O2 v/v) conditions but also in hypoxia (0.5% O2). With new compounds dissolved in the medium the cell photodamage in hypoxia was negligible whereas a significant photodamage was achieved with the emulsions of fluorinated porphyrins. The derivative with the fluoroalkyl substituent was more potent than its structurally close analog carrying the fluoroaryl moiety. CONCLUSION: Our new fluorinated porphyrin derivatives, especially their emulsions in which the photosensitizer and the oxygenated medium are coupled into one phase, can be perspective for photoelimination of hypoxic tumor cells.