From Nanocrystals and Nanocomposites to Microcrystals: The Role of Simonkolleite/ZnO in Overcoming Bacterial Resistance and Ensuring Biocompatibility.

This study presents the innovative application of simonkolleite (SM), its nanocomposite with ZnO nanocrystals (NCs), and ZnO nano-/microcrystals to explore their bactericidal and biocompatibility properties for potential biomedical applications. A systematic evaluation of antibacterial activity, antibiofilm efficacy, reactive oxygen species (ROS) production, and Drosophila melanogaster as an in vivo model was performed. The synthesis of SM, SM/ZnO nanocomposites (NCPs), and ZnO nano- and microcrystals was performed at different annealing temperatures: SM at 100 °C, SM/Zn NCPs (63.6% and 69.5% of ZnO NCs) at 250 and 500 °C, respectively, and ZnO NCs and microcrystals (MCs) at 500 and 1000 °C, respectively. Notably, ZnO NCs and MCs have demonstrated pronounced cytotoxicity in the D. melanogaster model, correlating with their ability to rapidly generate reactive oxygen species (ROS), contributing to oxidative stress and cellular damage. The SM/ZnO NCPs (250 °C) exhibited superior biocompatibility, suggesting that the SM partial conversion to ZnO may mitigate toxicity while retaining antimicrobial efficacy. Furthermore, subinhibitory concentrations of SM effectively inhibited biofilm formation, a critical factor in bacterial resistance, highlighting their potential applications in medical device coatings and antimicrobial therapies. Collectively, this research underscores the promising role of these materials in addressing antibiotic resistance and enhancing biocompatibility in biomedical applications.