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Pathogen and Graphene

Periodic Reporting for period 2 - PANG (Pathogen and Graphene)

Reporting period: 2018-01-01 to 2019-12-31

While complications related to infectious diseases have significantly reduced due to the availability of a broad-range of antibiotics and a wide variety of antimicrobial agents, the number of death related to infections is only declining every year by only 1 %, with a forecast of 13 million deaths due to these cases in 2050. While the development of vaccinations and novel anti-bacterial drugs and treatments are at the forefront of research, excessive use of antibiotics and antimicrobial agents increased significantly the number of multi-drug resistant (MDR) bacteria and has resulted in a serious threat to public health. According to published data in 2011, 25.000 patients die annually in the EU as a result of infections caused by antibiotic-resistant bacteria, with two thirds of these deaths due to Gram-negative pathogens. The costs incurred by drug resistant infections amount to an estimated €1.5 billion annually, due to increases in healthcare expenditure costs. The situation is all the more serious as antimicrobials have become an essential tool for modern medicine and many surgical operations could not be performed without them.
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. Among the various approaches, the use of nanomaterials is currently considered a highly promising strategy due to their small size, which allows packaging multiple antimicrobial agents on the same nanoparticle making the development of resistance unlikely. This project is thus exploring the utility of novel graphene based nanocomposites and surfaces 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-invasive therapies together with the understanding of the mechanism of action are the main focal points of the project entitled “PANG”, relating to Pathogen and Graphene.

The objectives of PANG are:
Objective I: Development of graphene-based antibacterial matrixes though chemical functionalization of these structures using antibacterial peptides and molecules (e.g. menthol and others) and test them for their toxicity and bactericidal potential (in particular against AMR strains)
Objective II: Use of the novel architectures in form of suspensions and transdermal patches for the killing of pathogens via non invasive photothermal therapy taking advantage of the good photothermal properties of rGO
Objective III: To get a deeper understanding of the effects of the novel structures on the immune system
Objective IV: To develop prototypes of antibacterial graphene matrixes and antibacterial transdermal patches with the SMEs involved in the project

The project impacts on science, society and economy in different ways. i) healthcare and well-being, ii) technology transfer and patenting, iii) formation of young researchers in truly interdisciplinary domain and iv) establishment of a network of knowledge.
Impact on science & technology: The field of treatment of bacterial skin infections and others with such structures is still in its infancy. Among the various approaches to fight multi-drug resistant (MDR) bacteria, the use of graphene matrixes and interfaces is an important alternative. The possibility of a combination of nanostructures with light activation in a photodynamic and/or photothermal approach to fight against infectious diseases is still not a routine used in hospitals.
The main deliverables and milestones of the project are
1. Development of a flexible skin patch allowing a rapid and highly efficient treatment of subcutaneous wound infections via photothermal irradiation. (published in ACS Applied Materials & Interfaces, 2017, 9 (42), pp 36665–36674)
2. Development of a novel nanofiber-based platform for photothermally-triggered “on-demand” release of antibiotics (published in ACS Applied Materials and Interfaces 2018, 10, 41098–41106)
3. Enhanced antibacterial activity of carbon quantum dots (CQDs) functionalized with ampicillin combined with visible light triggered photodynamic effects (published in Colloids and Surfaces B: Biointerfaces 2018, 170, 347-354)
4. Coetaneous skin patch for resale and storage of drug (patent application: Coetaneous device for storing and releasing molecules, and corresponding method, Sabine Szunerits et al. PCT application: EP19167905, 8 April 2019)
5 .Use of surface plasmon resonance (SPR) for the understanding the effect of of flow on pathogen binding mucins (published in Biosensors and Bioelectonics, 2019, 146, 111736)
Importantly, the visibility of the project also allowed the opening to other important research topics with following results
1. Use of graphene quantum dots (GQDs) for photoporation enabling homogenous labelling of live cells with extrinsic markers for fluorescence microscopy (published in Light: Science & Applications 2018, 7, 47)
2. Development of efficient nanostructures for next generation of vaccines (published in Materials Today 2019, 22, 58-66)
3. Use of functional carbon quantum dot as medical countermeasures to humancorona virus (HCoV) (published in ACS Applied Materials and Interfacs 2019, 11, 46, 42964-42974)