Bacterially synthesized ferrite nanoparticles for magnetic hyperthermia applications

Abstract

Magnetic hyperthermia uses AC stimulation of magnetic nanoparticles to generate heat for cancer cell destruction. Whilst nanoparticles produced inside magnetotactic bacteria have shown amongst the highest reported heating to date, these particles are magnetically blocked so that strong heating occurs only for mobile particles, unless magnetic field parameters are far outside clinical limits. Here, nanoparticles extracellularly produced by the bacteria Geobacter sulfurreducens are investigated that contain Co or Zn dopants to tune the magnetic anisotropy, saturation magnetization and nanoparticle sizes, enabling heating within clinical field constraints. The heating mechanisms specific to either Co or Zn doping are determined from frequency dependent specific absorption rate (SAR) measurements and innovative AC susceptometry simulations that use a realistic model concerning clusters of polydisperse nanoparticles in suspension. Whilst both particle types undergo magnetization relaxation and show heating effects in water under low AC frequency and field, only Zn doped particles maintain relaxation combined with hysteresis losses even when immobilized. This magnetic heating process could prove important in the biological environment where nanoparticle mobility may not be possible. Obtained SARs are discussed regarding clinical conditions which, together with their enhanced MRI contrast, indicate that biogenic Zn doped particles are promising for combined diagnostics and cancer therapy.

The cellular magnetic response and biocompatibility of biogenic zinc- and cobalt-doped magnetite nanoparticles

“…1c) and a complete loss in the χ’ signal beyond this value. This indicates a single dominating mode of relaxation which is expected to be Brownian relaxation for the magnetically blocked cobalt MNPs due to their high anisotropy2426. In contrast, both undoped synthetic magnetite and zinc-doped nanoparticles have an asymmetrical χ” peak with the real ( χ’ ) component greater than zero at higher frequencies.…”

“…The peaks in the χ” curves seen for the aqueous suspensions of the three different MNP types (Fig. 1a–c) are typical of a Brownian magnetisation relaxation process, with the frequency position of this peak depending on the hydrodynamic size of the particles26. Although the nanoparticle core sizes vary between samples depending on the level of doping2124, the similar positions of these χ” peaks in the ACS curves reveal comparable hydrodynamic particle/cluster sizes for all particle types (40–65 nm) (Table 1).…”

“…The sizes were calculated from ACS measurements for the nanoparticles in water using equation (1). The ACS technique has the advantage of measuring the hydrodynamic size of the particles based purely on their magnetic behaviour without interference by other non-magnetic2647 material not associated with the nanoparticle and hence was preferred over the DLS technique when possible. However, due to the very weak magnetism of CoFe 2 O 4 24 and Zn 0.9 Fe 2.1 O 4 21, their hydrodynamic sizes cannot be measured via ACS and were hence obtained from dynamic light scattering (DLS) measurements.…”

“…We have shown previously that ACS is an effective technique to non-invasively probe the magnetic response of nanoparticles in live cells2649. In this study, we measured the ACS signal in cells associated with either zinc or cobalt-doped biogenic nanoparticles, as well as undoped nanoparticles.…”

“…Analysis of these particles shows that they have a high degree of crystalline site ordering of the dopant cations25, leading to dramatic enhancements in either anisotropy in the case of cobalt dopants2324 or magnetic moment for zinc-doped particles21. We have also assessed the magnetisation relaxation effects and heating properties of these doped particles, with relevance to magnetic hyperthermia applications, and found differences in heating efficiencies between zinc- and cobalt-doped particles that depend on their degree of mobility26. However before these properties can be further utilised in biological environments it is necessary to assess the effect of the introduction of transition metal ions on the biocompatibility of the iron oxide core.…”