Trakia University – Stara Zagora is a partner in a European project aimed at combating tumor formations, ranked first with the highest score of 99.6% among a total of 82 proposals submitted for grant funding by the European Commission. The project, “Engineered erythrocytes and erythrocyte-derived extracellular vesicles for advanced photodynamic and sonodynamic therapy” (ERYSO), has a duration of four years.

The project is coordinated by the Association “Center for Cooperative Research in Biomaterials” (Spain). The consortium includes 12 partner organizations and universities from Italy, Germany, Israel, Argentina, Austria, Thailand, Indonesia, and Estonia, among them the Israel Institute of Technology – Technion, the University of Rome “Tor Vergata”, and Friedrich-Alexander University Erlangen–Nuremberg, among others.

The Bulgarian participation is represented by the team of Prof. Radostina Georgieva from the Faculty of Medicine at Trakia University – Stara Zagora. The invitation to take part in the project is based on the team’s long-standing experience in researching red blood cells (RBCs), the properties of their membranes, their capacity to be loaded with medicinal substances and magnetic nanoparticles, as well as their targeting of tumor cells through modification with antitumor antibodies and peptides.

The ERYSO project aims to develop innovative therapeutic solutions based on photodynamic (PDT), sonodynamic (SDT), and magnetothermal (MHT) therapy through the use of engineered red blood cells (RBCs) and extracellular vesicles (EVs) derived from them as multifunctional delivery platforms. Red blood cells and their derived extracellular vesicles transport hemoglobin—the body’s primary oxygen carrier—and are characterized by long circulation times, making them particularly suitable for therapeutic delivery.

By encapsulating photosensitizers and engineering these carriers to target tumor tissues, ERYSO overcomes one of the major limitations of current therapies—hypoxia in the tumor microenvironment—by delivering oxygen directly to hypoxic tumor regions and thereby enhancing therapeutic efficacy. The combination of photodynamic (PDT) and sonodynamic (SDT) therapies with magnetothermal (MHT) therapy further amplifies the therapeutic effect, providing a synergistic, multimodal approach to tumor eradication.

The combined therapeutic effect is achieved by encapsulating magnetic nanoparticles for magnetothermal therapy (MHT) or titanium dioxide nanoparticles for sonodynamic therapy within red blood cells (RBCs) or their derivatives—extracellular vesicles (EVs).

Tumor targeting will be achieved by functionalizing the outermost surface layer of red blood cells (the so-called glycocalyx) with targeting peptides or by incorporating functionalized lipids into the membranes of extracellular vesicles (EVs). Enhanced accumulation of RBCs and EVs in tumor tissue will be facilitated through the use of focused ultrasound (FUS) technology, which temporarily increases the permeability of the blood–tumor barrier.