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

Project description

Enhancing nanoparticle delivery by blocking macrophage uptake

Nanoparticles are engineered materials, small enough to travel through blood vessels and reach disease sites. For this reason, they have been used to carry medical drugs and imaging agents for diagnostics and therapy. However, accumulating evidence indicates that following administration most nanoparticles are cleared from blood vessels and taken up by macrophages in the liver and spleen. With the support of the Marie Skłodowska-Curie Actions programme, the RADBLOCK project aims to overcome this challenge and improve delivery of radioactive agents to tumours. Researchers propose a dual approach that involves nanoparticle modification with scaffold proteins that target HER2 receptors, found in aggressive breast and gastric cancers, and temporarily blocking the mononuclear phagocyte system.

Objective

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.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

UPPSALA UNIVERSITET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 252 180,00
Address
VON KRAEMERS ALLE 4
751 05 Uppsala
Sweden

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Region
Östra Sverige Östra Mellansverige Uppsala län
Activity type
Higher or Secondary Education Establishments
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Total cost

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