(269f) Eradication of Antibiotic-Resistant Biofilms By Hyperthermia Using Superparamagnetic Iron Oxide Nanoparticle Films

Implant-associated infections (IAIs) are a common complication associated with surgery failures. They are characterized by biofilm formation, which adhere to the surfaces of medical devices and are resistant against conventional antibiotic therapies. Therefore, there is a need to identify novel treatment strategies capable of killing established biofilms and/or prevent their formation (1). In this study, magnetic hyperthermia (MH) induced by superparamagnetic iron oxide nanoparticles (SPIONs) is used for biofilm eradication. SPIONs generate heat upon exposure to an alternating magnetic field (AMF), which can be used alone or in combination with conventional antibiotic therapies to induce biofilm eradication. The thermogenic bactericidal approach can facilitate an increased uptake of antibiotics to the bacterial cells and also overcome the limitations of chemical biocides that are susceptible to the differences in metabolic states of the bacteria. Here, implant surface coated with doped-SPION films were used to study the effect of MH on Staphylococcus aureus biofilm formation alone and in combination with vancomycin.

Manganese ferrite nanoparticles (Mn_0.5Fe_2.5O₄) of size 18 nm were in situ deposited during their production onto 10 mm x 10 mm silicon substrates using flame spray pyrolysis (2). These nanoparticles show higher saturation magnetization (67 emu g^-1) and magnetic hyperthermia (ΔT = 164 °C in 10 sec) than undoped SPIONs (3). Multiple Mn ferrite layers were deposited by encasing each layer in a polymer before the consecutive deposition. The nanoparticle composite film had a coating density of 1.3 mg cm^-2 and each nanoparticle film was 1.6 μm thick.

This study demonstrates that SPIONs can be successfully deposited on substrates and increase the surface temperature. The hyperthermia properties of the SPION film in combination with conventional antibiotics will be used to eradicate the biofilms of clinically relevant bacteria.

Acknowledgement: The authors would like to acknowledge the financial support from the Science for Life Laboratory. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 101002582)

References:

1. Alumutairi L, Yu B, Filka M, Nayfach J, Kim M-H. Mild magnetic nanoparticle hyperthermia enhances the susceptibility of Staphylococcus aureus biofilm to antibiotics. Int J Hyperth. 2020 Jan 1;37(1):66–75.

2. Sotiriou GA, Blattmann CO, Pratsinis SE. Flexible, Multifunctional, Magnetically Actuated Nanocomposite Films. Adv Funct Mater. 2013 Jan 7;23(1):34–41.

3. Ansari SR, Hempel N-J, Asad S, Svedlindh P, Bergström CAS, Löbmann K, et al. Hyperthermia-induced in situ drug amorphization by superparamagnetic nanoparticles in oral dosage forms. ChemRxiv. Cambridge: Cambridge Open Engage; 2022; This content is a preprint and has not been peer-reviewed.