Insight on the mechanisms of antimicrobial activity of metal and metal oxide nanoparticles and phototoxic enhancement by UV and daylight

The rising prevalence of multidrug-resistant pathogens poses a major global health threat, predicted to cause up to ten million deaths annually by 2050. Novel antimicrobial strategies are urgently needed, as the development of conventional therapeutics is at a critical shortage. Metal-based nanoparticles (NPs) represent a promising approach for infection prevention, with zinc oxide (ZnO), silver (Ag), and cerium dioxide (CeO₂) NPs receiving particular attention. The antimicrobial effects of these NPs are mediated through multiple mechanisms, including reactive oxygen species (ROS) generation, ion release, and membrane disruption. Ag NPs are often used as a reference in antimicrobial research because they are well studied and have broad efficacy. However, their potential cytotoxicity and environmental impact, resulting from ion release and NPs accumulation, raise significant concerns. Therefore, ZnO NPs, especially those produced by green synthesis, offer a promising alternative with potentially lower environmental impact and comparable antimicrobial efficacy. The underlying hypothesis is that green-synthesized ZnO NPs and CeO₂ NPs could serve as effective and environmentally compatible materials for surface coatings for infection prevention in comparison to Ag NPs serving as reference. For better understanding the materials, the following objectives were pursued: to study the underlying antimicrobial mechanisms and to properly determine their fields of application. Furthermore, it was hypothesized that the additional energy input upon exposure by daylight or UV-light can enhance the antimicrobial effects of NPs.To achieve the aims of this thesis a comprehensive methodological approach was employed. NPs were characterized, their antimicrobial mechanisms and parameters driving their efficacy were investigated, using Staphylococcus aureus (gram-positive), Escherichia coli (gram-negative), and Candida albicans (fungus) as model pathogens. For study their application as surface coatings, a chitosan-based membrane prototype incorporating ZnO NPs was developed and evaluated.Green-synthesized ZnO NPs showed strong antimicrobial activity, even surpassing the efficacy of Ag NPs against Staphylococcus aureus, with ROS generation identified as the dominant mechanism. This effect was enhanced by daylight and UV-light exposure. In contrast, CeO₂ NPs displayed minimal antimicrobial efficacy under the tested conditions. The chitosan-ZnO NP membrane demonstrated sustained inhibition of all three pathogens. Against Staphylococcus aureus and Escherichia coli an inhibition for over 24 hours and for Candida albicans over 20 hours was achieved, outperforming the individual NPs without being embedded into chitosan. Upon repeating the infection cycle (testing reusability of the membranes) only a partial inhibition was observed with this system.These findings highlight green-synthesized ZnO NPs as a sustainable and effective alternative to Ag NPs for infection prevention. The ZnO NPs-chitosan membrane system shows potential as a practical antimicrobial surface coating, although further testing, optimization, and validation is required, with a broader array of clinically relevant pathogens.