In the first twelve (12) months of the project there has been significant scientific and technological progress towards realizing the long term vision of bringing cold atmospheric pressure plasma to to the patient for the treatment of pancreatic and biliary cancer. Specifically:
Work Package 1 (WP1). CAP (Cold Atmospheric Pressure plasma) sources design, implementation. The first operating version of the plasma platform for the biological experiments (in SU) has been developed. Specifically, the hardware (i.e. mechanical, electrical, electronics, and optical components) and the software (multiple-microprocessor programming, graphic user interface / touchscreens, and closed loop schedule) of the plasma platform (both for the sinusoidal and pulsed versions) has been designed, while the sinusoidal version has been fully implemented and it is ready for testing. It is standalone and it can be adapted to meet the needs of diverse end-users in plasma biomedicine (for either basic research or/and industrial applications). It features close loop operation where the source can lock into one parameter (such as voltage, current, power, etc.) and keep it stable irrespective of the operating environment.
Work Package 2 (WP2).Therapeutic effect of CAP on preclinical cancer models. Using both ex vivo human liver slices and primary human epithelial cells, we demonstrated that CAP induces dose-dependent cytotoxicity, with greater sensitivity observed in tumor cells than in healthy hepatocytes and biliary epithelial cells. Notably, mesenchymal-like biliary cancer cells (HuCCT1) were more sensitive than epithelial-like ones (EGI-1), suggesting phenotype-dependent selectivity. Direct CAP exposure triggered DNA damage and apoptosis, while plasma-activated medium (PAM) had no cytotoxic effect on healthy cells, underscoring the role of non-chemical plasma components. In vivo/Ex vivo experiments on mice models showed that CAP significantly delayed tumor growth without visible skin damage or hazardous heating. However, reactive species (RONS) did not penetrate the skin barrier, highlighting its protective role. Efforts to establish real-time treatment monitoring identified temperature and surrogate markers as potential avenues.
Work Package 3: Plasma and cancer/host tissue in-silico models and digital interface. Developed two in silico models of coupled gas flow and plasma dynamics, a plasma-chemistry reduction mode, and an agent-based model for cancer cell dynamics. On the first leg of the modelling efforts, we have considerable progress where we are at the stage of the final validation tests of a 3D fluid dynamics / cold atmospheric plasma simulator that encompasses modelling the formation and propagation of streamer discharges while assuming a simplistic model of plasma chemistry. In parallel we have been developing a 2D-axisymmetric version of the above that accounts for a detailed description of the plasma chemistry. To bridge the two modelling approaches (the coarse-grained plasma chemistry but 3D geometry model versus the detailed plasma chemistry but 2D geometry model), and lead towards accelerating the computational efficiency of our in silico platform, we have built a Python-based plasma-chemistry reduction library, and we are at the stage of completing the validation and performance tests of our library. Finally, we develop an agent-based model to simulate the dynamics of (cancerous and host) cell, model the cell—cell and cell—matrix interactions, while also we are building ODE solvers to simulate intracellular processes as well as the effect of plasma reactive species on cell viability and cytotoxicity.
