Silica–gentamicin nanohybrids: combating antibiotic resistance, bacterial biofilms, and in vivo toxicity

Abstract

Dina A Mosselhy,1–3 Wei He,4 Ulla Hynönen,5 Yaping Meng,6 Pezhman Mohammadi,1 Airi Palva,5 Qingling Feng,7 Simo-Pekka Hannula,2 Katrina Nordström,1 Markus B Linder11Department of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, Espoo, Finland; 2Department of Chemistry and Materials Science, School of Chemical Engineering, Aalto University, Espoo, Finland; 3Fish Diseases Department, Microbiological Unit, Animal Health Research Institute, Dokki, Giza 12618, Egypt; 4School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, People’s Republic of China; 5Department of Veterinary Biosciences, Division of Veterinary Microbiology and Epidemiology, University of Helsinki, Helsinki, Finland; 6State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, People’s Republic of China; 7State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing, People’s Republic of China Introduction: Antibiotic resistance is a growing concern in health care. Methicillin-resistant Staphylococcus aureus (MRSA), forming biofilms, is a common cause of resistant orthopedic implant infections. Gentamicin is a crucial antibiotic preventing orthopedic infections. Silica–gentamicin (SiO2-G) delivery systems have attracted significant interest in preventing the formation of biofilms. However, compelling scientific evidence addressing their efficacy against planktonic MRSA and MRSA biofilms is still lacking, and their safety has not extensively been studied.Materials and methods: In this work, we have investigated the effects of SiO2-G nanohybrids against planktonic MRSA as well as MRSA and Escherichia coli biofilms and then evaluated their toxicity in zebrafish embryos, which are an excellent model for assessing the toxicity of nanotherapeutics.Results: SiO2-G nanohybrids inhibited the growth and killed planktonic MRSA at a minimum concentration of 500 µg/mL. SiO2-G nanohybrids entirely eradicated E. coli cells in biofilms at a minimum concentration of 250 µg/mL and utterly deformed their ultrastructure through the deterioration of bacterial shapes and wrinkling of their cell walls. Zebrafish embryos exposed to SiO2-G nanohybrids (500 and 1,000 µg/mL) showed a nonsignificant increase in mortality rates, 13.4±9.4 and 15%±7.1%, respectively, mainly detected 24 hours post fertilization (hpf). Frequencies of malformations were significantly different from the control group only 24 hpf at the higher exposure concentration.Conclusion: Collectively, this work provides the first comprehensive in vivo assessment of SiO2-G nanohybrids as a biocompatible drug delivery system and describes the efficacy of SiO2-G nanohybrids in combating planktonic MRSA cells and eradicating E. coli biofilms.Keywords: SiO2, gentamicin, MRSA, antibacterial and antibiofilm effects, nanotoxicity, zebrafish

Keywords

• SiO2
• gentamicin
• MRSA
• antibacterial and anti-biofilm effects
• nanotoxicity
• zebrafish