Descripción del proyecto
Portadores innovadores para terapia fotodinámica más eficiente
La terapia fotodinámica (TFD) implica la utilización de un fármaco que se activa mediante la luz para matar las células cancerosas. La presencia de oxígeno es fundamental para la generación de especies radicales de oxígeno, los cuales provocan la muerte de las células tumorales. Uno de los principales obstáculos de la TFD en el cáncer es la hipoxia del tejido tumoral. El equipo del proyecto OXIGENATED, financiado por las Acciones Marie Skłodowska-Curie, pretende desarrollar nanoportadores para la administración medicamentos basados en la hemoglobina (HDDN, por sus siglas en inglés) para la administración simultánea de oxígeno y del fotosensibilizador en el tejido tumoral para una TFD eficiente. Los HDDN transportarán oxígeno complejado con hemoglobina con las moléculas del fotosensibilizador atrapadas en el núcleo. Se realizarán pruebas «in vitro» de la absorción de los HDDN por parte de las células, así como del destino intracelular y de la toxicidad. Los estudios «in vivo» con ratones trazará portadores radioetiquetados mediante tomografía.
Objetivo
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.
Ámbito científico
- natural scienceschemical sciencesinorganic chemistryinorganic compounds
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicineoncology
- engineering and technologyother engineering and technologiesmicrotechnologymolecular engineering
- natural sciencesbiological sciencesmolecular biology
Palabras clave
Programa(s)
Régimen de financiación
MSCA-RISE - Marie Skłodowska-Curie Research and Innovation Staff Exchange (RISE)Coordinador
20009 San Sebastian
España