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.

Fluorescent boron difluoride curcuminoides as perspective materials for bio-visualization.

Curcuminoids of boron difluoride, 1-aryl(hetaryl)-5-phenylpenta-2,4-dien-1-onates of boron difluoride, have been synthesized. A comparative study of the electronic structure, luminescent properties and their potential for applications in bio-imaging has been carried out. The influence of the electronic structure of α-substituents on the luminescence of compounds was studied by the methods of stationary and time-resolved luminescence spectroscopy and DFT modeling. The introduction of π-donor substituents leads to a noticeable bathochromic shift and an increase in the Stokes shift in the luminescence spectra. On going from σ-donor substituents in the phenyl ring to π-donor substituents, the luminescence quantum yield increases from 0.03 to 0.22. The maximum Stokes shift and high quantum yield of luminescence is exhibited by the complex with a stilbene substituent, which has the longest π-system and the maximum efficiency of charge transfer. Dyes are able to penetrate into the cells of the model cell line and accumulate, moreover, accumulation occurs mainly in the cytoplasm of cells. The compounds penetrate into the cells by 12 h of incubation without damaging it's structure and without causing rapid cell death. The submicromolar range of non-toxic concentrations during long-term incubation for a model cell line was determined, which is a characteristic of fluorescent imaging. Due to uniform distribution in the cytoplasm of cells dye with naphtyl substituent is promising for visualization of the cell cytoplasm. This leader compound has the lowest cytotoxicity for cells from the synthesized series of dyes, which makes it promising for further studies as a fluorescent imaging agent. The leader compound has the lowest cytotoxicity for cells from the synthesized series of dyes, which makes it promising for further studies as a fluorescent imaging agent.

Benzylidene Cyclopentanone Derivative Photoinitiator for Two-Photon Photopolymerization-Photochemistry and 3D Structures Fabrication for X-ray Application.

Micron- and submicron-scale 3D structure realization nowadays is possible due to the two-photon photopolymerization (TPP) direct laser writing photolithography (DLW photolithography) method. However, the achievement of lithographic features with dimensions less than 100 nm is in demand for the fabrication of micro-optical elements with high curvature values, including X-ray microlenses. Spectroscopic and photochemical study of a photoinitiator (PI) based on a methyl methacrylate derivative of 2,5-bis(4-(dimethylamino)benzylidene) cyclopentanone was performed. Enhanced intersystem crossing in the methyl methacrylate derivative results in increased radical generation for the subsequent initiation of polymerization. A comprehensive study of the new photocompositions was performed, with particular emphasis on photochemical constants, the degree of photopolymerization, and topology. The optimal parameters for the fabrication of mechanically stable structures were determined in this research. The threshold dose parameters for lithography (radiation power of 5 mW at a speed of 180 µm/s) when trying to reach saturation values with a conversion degree of (35 ± 1) % were defined, as well as parameters for sub-100 nm feature fabrication. Moreover, the 45 nm feature size for elements was reached. Fabrication of X-ray lens microstructures was also demonstrated.