Opis projektu
Nowe leki metalowo-peptydowe do terapii fotodynamicznej nowotworów
Terapia fotodynamiczna nowotworów polega na wykorzystaniu światła do aktywacji leków, które w innym przypadku są obojętne. Pozwala to ograniczyć toksyczność, ponieważ zapewnia, że leki niszczą guz, a nie zdrowe komórki. Jednak problemy z penetracją przez światło, niedotlenieniem guza i słabym wychwytem leku przez komórki nowotworowe utrudniają sukces terapii fotodynamicznej. Zespół projektu pepRu4PACT, finansowanego przez działania „Maria Skłodowska-Curie”, opracuje leki na bazie metali, które są aktywowane przez podczerwień lub bliską podczerwień. Takie związki rutenu działają w warunkach niskiej zawartości tlenu. Zostaną sprzężone z peptydami przeciwnowotworowymi, aby zwiększyć wychwyt proleku przez komórki nowotworowe.
Cel
One of the most severe limitations of current anticancer chemotherapy are the serious side effects caused by toxic drugs affecting not only tumors but also healthy organs. Local activation of drugs by light irradiation of the tumor is a promising approach to control where the toxicity is delivered. Metal complexes are well suited for photoactivated chemotherapy, but their activation wavelength is often too low to afford high tissue penetration of light; also, their ability to enter cancer cells is often controlled by lipophilicity tuning, which is unselective; finally, their phototoxicity often relies on oxygen-dependent mechanisms, while many tumor tissues show low dioxygen concentrations.
The aim of this proposal is to develop new metallodrugs that are activated by red or near-infrared light, enter cells by controlled mechanisms, and deliver strong phototoxicity to cancer cells also under low oxygen conditions. The design is based on connecting multiple Ru(II) metal complexes to a biologically active antitumoral peptide. The ruthenium complexes will have a tuned coordination environment to allow red/near-IR light activation; meanwhile, the peptides will rely on methionine residues to coordinate ruthenium, and allow controlled cellular uptake of the prodrug into cancer cells. Both components will cage each other in the dark, thus affording low toxicity; while light-induced cleavage of the ruthenium-thioether bonds will release two bioactive components, which will kill cancer cells.
The novelty of this proposal is to combine metal-based photoactivated chemotherapy with therapeutic peptides to enhance phototoxicity by creating synergies between both photoproducts. By combining light activation, resulting in timely- and spatially-resolved toxicity release, and bioactive peptides, which will improve uptake in cancer cells, this project will deliver new fundamental knowledge on the interaction between peptides and metals, and between metallopeptides and cells.
Dziedzina nauki
Program(-y)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Zaproszenie do składania wniosków
Zobacz inne projekty w ramach tego zaproszeniaSystem finansowania
HORIZON-AG-UN - HORIZON Unit GrantKoordynator
2311 EZ Leiden
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