Nanodispersed carriers, tetrapyrroles, molecular aggregates, hybrid systems, photosensitizers

Abstract:

The main goal of the project is the creation of new hybrid systems using nanodispersed carriers that allow selective stabilization of monomeric, dimeric or aggregated forms of tetrapyrrole compounds that intensively absorb light in the 700-850 nm range and have fluorescence and photochemical activity. Specific applications of such systems depend on the type of photochemical properties, first of all, exhibit-highly selective luminescent visualization of cells and effective photodynamic processes, such as energy transfer or electron transfer. The novel created hybrid systems will be characterized by a complex of modern physicochemical methods.
The project is expected to be implemented in two phases.
In 2018-1019, synthesis and detailed study of photophysical characteristics of hybrid systems based on nanoparticles, dimers and molecular aggregates of tetrapyrroles will be carried out. For novel systems, the laws and efficiency of electron and energy phototransfer and the parameters characterizing their fluorescence will be determined. In 2020, the complexity of objects (the modification of tetrapyrroles and nanodispersed carriers) will be realized for increasing the bioavailability and specificity of their photochemical effects on cells. The most promising systems will be tested on cell lines.

First year results:

At the first stage of the project, a number of new hybrid supramolecular systems based on nanoparticles (SiO2, PLGA, nanoclay) and model micellar and polymer systems with a selective stabilization of the certain forms of tetrapyrrolic compounds (monomer, dimmer, J- or H-type aggregates) were obtained. For the above systems, the aggregation state of the tetrapyrroles was established, the main photophysical parameters were determined and the particle size and morphology were characterized. For the photoactive systems, the type of the predominant photochemical activity was established: photosensitization (by the energy transfer mechanism), photocatalytic activity (by the electron transfer mechanism) or radiative excited state deactivation via fluorescence. Supramolecular systems with catalytic activity in the generation of ROS were tested for antitumor activity against three cancer cell lines and were shown to possess twice as high cytotoxicity as compared with the free tetrapyrroles.

See PDF: rfbr-2018

Second year results:

The aim of the project is design of photoactive hybrid supramolecular systems based on nanocarriers of mineral and organic nature and tetrapyrrolic compounds, providing the control over their photophysical properties and the type of photochemical activity at the supramolecular level without any covalent modifications of the components. During the second year of the project realization, the most promising combinations of nanodispersed carriers (model micellar systems, polymer nanoparticles and polyelectrolyte complexes, nano-SiO₂) and tetrapyrrolic compounds (amphiphilic meso-arylporphyrins and various chlorin e₆ derivatives) have been selected. In such supramolecular systems the main photophysical parameters of tetrapyrroles (the energy of electronic transitions, extinction coefficients and fluorescence quantum yields) have been determined, and the photochemical activity in the singlet oxygen generation has been estimated. The predominant type of molecular aggregates formed has been established from the spectral data. For some systems, localization area of the tetrapyrroles within the micellar systems has been evaluated using spin probe EPR spectroscopy. For all the nanodispersed systems hydrodynamic radius and zeta-potential on the particle surface have been measured. As a result, a number of the most prospective systems have been selected for the further biological studies in the tumor cell cultures.

See PDF: RFBR-2019