Macrophage blockade for the improvement of targeted radionuclide delivery to malignant tumours

The aim of RADBLOCK is to improve nanocarrier-based radionuclide delivery by enhancing targeting and overcoming problem of non-specific uptake of nanoparticles by macrophages in liver and spleen. For this purpose, two approaches will be used simultaneously: 1) modification of radionuclide-loaded nanoparticles with targeted scaffold proteins, recognizing HER2 receptor expressed by malignant cells; 2) temporal blockade of the cells of the mononuclear phagocyte system (MPS) to decrease elimination of the nanocarrier. The results of the project will be beneficial to the diagnostics and treatment of tumours with overexpression of HER2 receptors, such as human breast and gastric/gastroesophageal carcinomas. This project is novel and innovative, since presents first application of macrophage blockade technology for improving of radionuclide delivery with nanoparticles. RADBLOCK is a multidisciplinary project and combines modern chemical methods of nanocarrier preparation, physical methods for the material analysis and its comprehensive biological evaluation at the animals, bearing human xenografts. The applicant will conduct research in Uppsala University under supervision of Prof. Vladimir Tolmachev, expert in radiopharmaceutics and clinical applications of targeted scaffold proteins. As a two-way knowledge transfer fellow will be trained in methods of radiochemistry and radiopharmaceutics and will bring experience with nanomaterials chemistry and macrophage blockade techniques to the host organization. RADBLOCK is expected to increase radionuclide blood bioavailability in mammals and enhance specific tumour delivery, which will have positive effects on targeted diagnostics and therapy of malignant tumours with radionuclides.