Descrizione del progetto
Vettori innovativi per migliorare l’efficienza della terapia fotodinamica
La terapia fotodinamica comporta l’utilizzo di un farmaco che viene attivato dalla luce per eliminare le cellule tumorali. Per generare le specie di ossigeno radicale che provocano la morte delle cellule tumorali, è essenziale la presenza di ossigeno. Un ostacolo importante all’applicazione oncologica della terapia fotodinamica è l’ipossia nel tessuto tumorale. L’obiettivo del progetto OXIGENATED, finanziato dal programma di azioni Marie Skłodowska-Curie, è quello di sviluppare nanovettori per la somministrazione farmacologica a base di emoglobina per fornire simultaneamente al tessuto tumorale ossigeno e fotosensibilizzante, al fine di rendere più efficiente la terapia fotodinamica. Questi nanovettori trasporteranno ossigeno complessato con emoglobina con le molecole di fotosensibilizzante racchiuse nel nucleo. Ne saranno testati in vitro l’assorbimento da parte delle cellule, il loro destino intracellulare e la tossicità. Studi in vivo sui topi tracceranno i vettori radiomarcati per mezzo della tomografia.
Obiettivo
A major drawback of Photodynamic Therapy (PDT) and other therapies for cancer treatment is the limited oxygen content, hypoxia, in tumour tissue. In PDT a photosensitizing molecule is delivered to malignant tissue to generate radical oxygen species (ROS). The presence of oxygen is fundamental for ROS generation, ultimately causing the death of tumour cells.
This project aims to develop hemoglobin drug delivery nanocarriers in the nano and submicron range for simultaneous oxygen and photosensitizer delivery to tumour tissue for a more efficient Photodynamic Therapy.
Hemoglobin-based nanocarriers (HOBCs) will be prepared by co-precipitation of hemoglobin with carbonates and surface coating with bovine serum albumin. The carriers will transport oxygen complexed to hemoglobin while photosensitizer molecules will be entrapped in the core. Carriers will be modified with homing peptides to target them to cancer cells. In vitro studies will be conducted to study the uptake of HOBCs by cells, their intracellular fate, toxicity, and oxygen and photosensitizer delivery. In vivo fate of carriers will be studied in mice with radiolabeled carriers by Positron Emission Tomography and Single Emission Computer Tomography. The efficiency of the HOBCs for oxygen delivery and for PDT will be tested in vitro and in vivo in breast and skin cancer models.
A multidisciplinary team has been gathered with scientists at the forefront of Material Science, Self assembly, Physics, Chemistry, Imaging, Molecular Biology and Cancer Therapy from Germany, Estonia, Spain, Brazil, Argentina and Thailand. The participation of a SME will be fundamental for the future commercialization of project developments. OXIGENATED will actively work towards exchanging skills and knowledge through secondments of Early Stage and Experienced Researchers, and through networking and training activities. Seconded researchers will develop new scientific and complementary skills while exposed to new research environments.
Campo scientifico
- natural scienceschemical sciencesinorganic chemistryinorganic compounds
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicineoncology
- engineering and technologyother engineering and technologiesmicrotechnologymolecular engineering
- natural sciencesbiological sciencesmolecular biology
Parole chiave
Programma(i)
Meccanismo di finanziamento
MSCA-RISE - Marie Skłodowska-Curie Research and Innovation Staff Exchange (RISE)Coordinatore
20009 San Sebastian
Spagna