Description du projet
Des vecteurs innovants pour une thérapie photodynamique plus efficace
La thérapie photodynamique (TPD) implique l’utilisation d’un médicament qui est activé par la lumière pour tuer les cellules cancéreuses. La présence d’oxygène est cruciale pour la génération d’espèces radicalaires d’oxygène, qui provoquent la mort des cellules tumorales. L’hypoxie dans les tissus tumoraux constitue un obstacle majeur à la TPD du cancer. Financé par le programme Actions Marie Skłodowska-Curie, le projet OXIGENATED a pour objectif de développer des nanotransporteurs de médicament à base d’hémoglobine (HDDN) pour l’administration simultanée d’oxygène et de photosensibilisateur au tissu tumoral, pour une TPD efficace. Les HDDN transporteront l’oxygène complexé à l’hémoglobine tandis que les molécules de photosensibilisation seront piégées dans le noyau. L’absorption des HDDN par les cellules sera testée in vitro, tout comme leur destin intracellulaire et leur toxicité. Des études in vivo menées sur des souris permettront de tracer des vecteurs radiomarqués grâce à la tomographie.
Objectif
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.
Champ scientifique
- natural scienceschemical sciencesinorganic chemistryinorganic compounds
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicineoncology
- engineering and technologyother engineering and technologiesmicrotechnologymolecular engineering
- natural sciencesbiological sciencesmolecular biology
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Programme(s)
Régime de financement
MSCA-RISE - Marie Skłodowska-Curie Research and Innovation Staff Exchange (RISE)Coordinateur
20009 San Sebastian
Espagne