Complications related to infectious diseases have significantly reduced, particularly in the developed countries, due to the availability and use of broad-range antibiotics and wide variety of antimicrobial agents. Excessive use of antibiotics and antimicrobial agents increased significantly the number of multi-drug resistant (MDR) bacteria. This has resulted in a serious threat to public health. The inexorable rise in the incidence of antibiotic resistance in bacterial pathogens, coupled with the low rate of emergence of new clinically useful antibiotics, has refocused attention on finding alternatives to overcome antimicrobial resistance. Novel strategies aiming to reduce the amount of antibiotics, but able to prevent and treat animal and human infections should be investigated, evidenced and approved. Among the various approaches, the use of graphene and its derivatives is currently considered a highly promising strategy to overcome microbial drug resistance. In line with this interest in graphene by the European Commission through the graphene ‘flagship’ initiatives, we respond in this consortium by exploring the utility of novel graphene based nanocomposites for the management and better understanding of microbial infections. The anti-microbical potential of the novel graphene based nanomaterials, the possibility of using such structures for the development of non-invase therapies together with the understanding of the mechanism of action will be the main focal points of the proposed project entitled “PANG”, relating to Pathogen and Graphene. We have gathered the essential elements, namely different academic institutions in Europe (France, Germany, and Sweden) and their associated countries (Ukraine) as well as two European companies (Graphenea-Spain and LSO Medical-France) and one company (RS RESEARCH) in one of the associated countries (Turkey). The proposed multidisciplinary project uniquely suits high-level interdisciplinary and cross-border training.

Reactive oxygen species (ROS) have key functions in healthy organism such as redox signaling for regulation of cell growth, triggering formation of neutrophil extracellular traps (NETs), and modulation of inflammation. Since in high concentration ROS are damaging to tissues, nature has evolved precise mechanisms to control their generation at the required time, concentration and space, proximal to their target. Disturbance of these mechanisms leads to aberrant ROS production that causes uncontrolled inflammation, occurs in myeloablation caused by radio- or chemotherapy and is a crucial feature of cancer cell phenotype as well as autoimmunity. Despite the damaging properties of ROS it is a paradox that pharmaceutical ROS amplifiers can reverse (“cure”) many pathologic features. For example, ROS-induced cancer cell killing inhibits cancer growth, ROS-induced deactivation of T-cells and NETs generation contributes to resolution of inflammation, and ROS-induced boosting of haematopoiesis can relieve myeloablation. These exciting possibilities have not been realized in clinical settings yet, since the high level of temporal and spatial control of ROS generation, required to allow for safe patient treatment, has yet not been achieved for any known drug. NeutroCure will be the first attempt to achieve a breakthrough solution to this problem. Using an innovative approach based on the multiple-trigger prodrug activation, this consortium will develop safe ROS amplifiers capable of boosting ROS specifically in abnormal polymorphonuclear neutrophils associated with cancer, uncontrolled inflammation and relevant for myeloablation without affecting normal cells. NeutroCure consists of 6 European academic partners and an SME who will promote commercialization of the new drugs. We expect that this project will have a great positive impact on the Society by providing previously unexplored treatment solutions for severe pathological conditions caused by dysregulated ROS-production.