Objective
In recent years photodynamic therapy (PDT) has been extensively developed in various countries for treatment of certain types of cancer and skin diseases. PDT is based on the use of natural or synthetic photosensitizers, which, because of their specific chemical structure, are capable of accumulating in cancerous tissues. In the clinical therapy of cancer some drugs based on hematoporphyrin-IX, are used as photosensitizers. There are, however, some problems associated in their use, such as prolonged cutaneous phototoxicity, photodegradation during illumination and weak absorption of light in the region of the highest tissue transparency. These limitations have prompted a search for alternative PDT photosensitizers.
The present inter-disciplinary project focuses on inorganic semiconductor nanocrystals (SNs) as potential photosensitizers for PDT of various cancerous and skin diseases. Semiconductor nanocrystals, whose particle size is comparable to that of organic dye molecules, are capable, just as bulk semiconductors, to produce electrons and holes in the conduction and valence bands upon bandgap illumination. These charge carriers have been demonstrated to be very active towards oxidizable and reducible substrates. In addition, semiconductor nanocrystals are likely to be more active and stable than organic photosensitizers.
We intend to use different peptides, proteins and ferritin as templates and capped agents for CdS, CdSe, FeS2, InAs, InP, Fe203 and other semiconductor nanocrystals synthesis. These peptide- or protein-capped SNs, absorbing light in a wide spectral range (up to lambda = 900 nm), would be able to photosensitize various destruction processes in the cells. In addition, peptide- and protein-capped Fe203 SNs and complexes of the iron-storage protein ferritin with SNs under the action of light are a viable source of Fe2+ ions which is capable of initiating chain oxidation processes and more generally to participate in catalytic oxidation processes in oxygenated media.
The main objectives of the project are:
1) to obtain peptide and protein-capped nanocrystals of inorganic semiconductors absorbing light in the tissue transparency region (e.g. lambda = 600-900 nm);
2) to investigate the mechanisms and dynamics of photoinduced electron transfer processes occurring between SNs complexes and species in aqueous solution;
3) to study the photocatalytic properties of peptide- or protein-capped SNs;
4) to determine the conditions of the photodissolution of ferric oxide/hydroxide nanocrystals capped with peptides and proteins and of ferric hydroxide nanocrystals found in the interior of ferritin with their concomitant production of Fe2+ ions;
5) to study the processes of destruction of biomolecules, cells and subcellular structures upon photosensitization by peptide- and protein-capped SNs;
6) to elucidate the chemical mechanism of the destruction processes sensitisation under laser pulse excitation; and finally,
7) to study the photosensitizing action of peptide- and protein-capped SNs on different types of human tumor cell lines; to provide the specific delivery of SNs to tumor cells using conjugates of SNs with antiferritin antibodies and biotinylated antibodies with avidin.
The studies of the processes of destruction of biomolecules, subcellular structures and tumor cells photosensitized by will allow knowledgeable recommendations for the use of this type of sensitizer in cancer treatment. Obtained results will also be of a very broad interest in physical chemistry and biology as they will contribute to the understanding of the mechanisms and dynamics of electron transfer processes taking place in artificial and biological systems containing inorganic semiconductors and proteins.
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Programme(s)
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Coordinator
1015 Lausanne
Switzerland
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