Atmospheric pressure plasma jets generate reactive oxygen and nitrogen species (RONS) in liquids and biological media, which find application in the new area of plasma medicine. These plasma-treated liquids demonstrated recently to possess selective properties on killing cancer cells and attract attention towards new plasma-based cancer therapies. These allow for local delivery by injection in the tumor but can be quickly washed away by body fluids. By confining these RONS in a suitable biocompatible delivery system, great perspectives can be opened in the design of novel biomaterials aimed for cancer therapies. Gelatin solutions are evaluated here to store RONS generated by atmospheric pressure plasma jets, and their release properties are evaluated. The concentration of RONS was studied in 2% gelatin as a function of different plasma parameters (treatment time, nozzle distance and gas flow) with two different plasma jets. Much higher production of reactive species (H 2 O 2 and NO 2-) was revealed in the polymer solution than in water after plasma treatment. The amount of RONS generated in gelatin is greatly improved with respect to water, with concentrations of H 2 O 2 and NO 2between 2 and 12 times higher for the longest plasma treatments. Plasma-treated gelatin exhibited the release of these RONS to a liquid media, which induced an effective killing of bone cancer cells. Indeed, in vitro studies on Sarcoma Osteogenic (SaOS-2) cell line exposed to plasma-treated gelatin lead to timedependent increasing cytotoxicity with the longer plasma treatment time of gelatin. While SaOS-2 cell viability decreased down to 12%-23% after 72 hours for cells exposed to 3-min treated gelatin, viability of healthy cells (hMSC) was preserved (around 90%), establishing the selectivity of the plasma-treated gelatin on cancer cells. This sets the basis for designing improved hydrogels with high capacity to deliver RONS locally to tumors.
This work is a contribution to the development and implementation of non-thermal plasma technology for decontamination in the perspective of nosocomial and chronic wound innovative therapies. Multi jets devices based on Plasma Gun® technology in static and scanning operation modes and bacterial lawns inoculated with resistant and non-resistant bacterial strains were designed and used. A pilot toxicity study exploring plasma treatment of wound bearing patients, performed with a low voltage plasma applicator, is documented as a first step for the translation of in vitro experiments to clinical care. Bacterial inactivation was demonstrated for Staphylococcus aureus, Pseudomonas aeruginosa and drug resistant S. aureus, P. aeruginosa and Escherichia Coli strains collected from patient wounds at Orleans (France) hospital. A few square centimeter large contaminated samples were inactivated following a single plasma exposure as short as one minute. Samples inoculated with a single but also a mix of three resistant pathogens were successfully inactivated not only right after their contamination but for mature lawns as well. Similar bactericidal action was demonstrated for antibiotic-resistant and non-resistant P. aeruginosa. The time exposure dependent increase of the inhibition spots, following multi jets exposure, is discussed as either the accumulation of reactive species or the likely combinatory action of both the reactive species and transient electric field delivery on inoculated samples.
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