Macromolecular toolbox for biomedical applications

Project facts

Project promoter:
Institute of Macromolecular Chemistry AS CR
Project Number:
CZ09-0001
Target groups
Researchers or scientists
Status:
Completed
Initial project cost:
€964,100
Final project cost:
€884,464
From Norway Grants:
€ 601,435
The project is carried out in:
Praha

Description

This project is devoted to develop innovative macromolecular nanoparticulate toolbox system, consisting of a new generation self-organized polymer-based materials that could be used for biomedical applications in cancer, tuberculosis and inflammation treatment. It will exploit the expertise and complementarity of five well-established research groups, two Czech and three Norwegian. The tools consist of biodegradable polymerc nanoparticles. After characterization of the particles, their surface will be covered by a polymer that carries: (a) groups targeting specific receptors on theranostic target, (b) active therapeutic groups, (c) groups allowing complexation of the polymer to the nanoparticle. The size of the particles will be in the range 50-200 nanometers allowing advantage of the enhanced permeability and retention effect. Finally, the new systems will be tested for their anti-cancer activity and anti-bacterial and anti-inflammatory activity using in vitro cell cultures and in vivo models of the diseases.

Summary of project results

This project is devoted to develop an innovative modular nanoparticulate toolbox system, consisting of a new generation of self-organized polymer-based materials that could be used for biomedical applications in cancer, tuberculosis and inflammation treatment. It exploits the expertise and complementarity of four well-established research groups, two Czech and two Norwegian. The tools consisted of biodegradable polymeric nanoparticles (synthesized and prepared at Department of Chemistry (DC), University of Oslo). After characterization of the particles (at DC, University of Oslo), their surface was covered by a polymer (synthesized at Institute of Macromolecular Chemistry AS CR in Prague) that carries: (a) groups targeting specific receptors on theranostic target, (b) active therapeutic groups, (c) groups allowing complexation of the polymer to the nanoparticle. The size of the particles is in the range 50-200 nanometers allowing to take advantage of the enhanced permeability and retention (EPR) effect. Finally, the new systems were tested for their anti-cancer activity (at Department of Tumor Biology, University of Oslo Hospital), using in vitro cell cultures (prepared at 1st Medical Faculty, Charles University in Prague) and in vivo models of the diseases. The project objectives are to make compounds for the creation of a modular system based on polymeric materials for successful treatment of cancer, tuberculosis, and inflammation. By easy modulation of surface properties, the polymer nanoparticles could be recognized or not-recognized by macrophages that determine the way of the potential treatment. The final results consist of nanostructures with unprecedented possibility of fine-tuning: adjustable size in suitable range, temperature- and pH-sensitivity, suitable targeting moieties on the surface and ability to release active components in a controlled way. In addition, the same type of systems may be used not only for targeted delivery and controlled release of therapeutics, but also for simultaneous diagnostic imaging. This allows for therapeutic feedback allowing further customization of the treatment.

Summary of bilateral results

The beneficiaries were involved in efficacy of the nanoparticle drug delivery systems fine-tuned for cancer and TB treatment was demonstrated in vitro and in vivo on animal models. This was an excellent starting point to further pass into advanced preclinical and clinical testing and introduction of these system to clinical practice. IMC Prague contributed to (Bio)functionalization of the polyester nanoparticles that were synthesized and fine-tuned by DC Oslo. DC Oslo did synthesis and characterization of fully biodegradable polymer nanoparticles with minimal cytotoxicity. CUNI Prague carried out experiments with in vitro cultured cells while using sophisticated microscopies. Biological evaluation of the nanoparticles designed to treat Mycobacterium sp. infections and NRH Oslo completed an evaluation nanoparticulate systems in vivo in murine models of human cancers. The partnership has allowed achievement of the multidisciplinary outputs joining specific skills of the project partners (IMC Prague, DC Oslo – chemistry and physics) and biology (CUNI Prague – microscopy, tuberculosis), NRH Oslo (cancer). The partnership has achieved solving the project established a long-term collaboration of the project partners and led to proposing next common project proposals and publications. Through the presentations at the various public events listed below the active participants and attendees from general public increased their awareness about tuberculosis and cancer diseases and about issues and difficulties related to treatment of these conditions. Close cooperation between biologists, chemists and physicists involved in the project increased the level of mutual scientific understanding between members of these communities.