Biodegraded magnetosomes with reduced size and heating power maintain a persistent activity against intracranial U87-Luc mouse GBM tumors.

BACKGROUND: An important but rarely addressed question in nano-therapy is to know whether bio-degraded nanoparticles with reduced sizes and weakened heating power are able to maintain sufficient anti-tumor activity to fully eradicate a tumor, hence preventing tumor re-growth. To answer it, we studied magnetosomes, which are nanoparticles synthesized by magnetotactic bacteria with sufficiently large sizes (~ 30 nm on average) to enable a follow-up of nanoparticle sizes/heating power variations under two different altering conditions that do not prevent anti-tumor activity, i.e. in vitro cellular internalization and in vivo intra-tumor stay for more than 30 days. RESULTS: When magnetosomes are internalized in U87-Luc cells by being incubated with these cells during 24 h in vitro, the dominant magnetosome sizes within the magnetosome size distribution (DMS) and specific absorption rate (SAR) strongly decrease from DMS ~ 40 nm and SAR ~ 1234 W/gFe before internalization to DMS ~ 11 nm and SAR ~ 57 W/gFe after internalization, a behavior that does not prevent internalized magnetosomes to efficiently destroy U87-Luc cell, i.e. the percentage of U87-Luc living cells incubated with magnetosomes decreases by 25% between before and after alternating magnetic field (AMF) application. When 2 µl of a suspension containing 40 µg of magnetosomes are administered to intracranial U87-Luc tumors of 2 mm3 and exposed (or not) to 15 magnetic sessions (MS), each one consisting in 30 min application of an AMF of 27 mT and 198 kHz, DMS and SAR decrease between before and after the 15 MS from ~ 40 nm and ~ 4 W/gFe down to ~ 29 nm and ~ 0 W/gFe. Although the magnetosome heating power is weakened in vivo, i.e. no measurable tumor temperature increase is observed after the sixth MS, anti-tumor activity remains persistent up to the 15th MS, resulting in full tumor disappearance among 50% of treated mice. CONCLUSION: Here, we report sustained magnetosome anti-tumor activity under conditions of significant magnetosome size reduction and complete loss of magnetosome heating power.

Ferromagnetic resonance spectra of linear magnetosome chains.

The ferromagnetic resonance (FMR) spectra of oriented and non-oriented assemblies of linear magnetosome chains are calculated by solving the stochastic Landau-Lifshitz equation. The dependence of the shape of the FMR spectrum of a dilute assembly of chains on the particle diameter, the number of particles in a chain, the distance between the centers of neighboring particles, the mutual orientation of the cubic axes of particle anisotropy, and the value of the magnetic damping constant is studied. It is shown that FMR spectra of non-oriented chain assemblies depend on the average particle diameter at a fixed thickness of the lipid magnetosome membrane, as well as on the value of the magnetic damping constant. At the same time, they are practically independent of the number Np of particles in the chain under the condition Np ≥ 10. The FMR spectra of non-oriented assemblies of magnetosome chains are compared with that of random clusters of interacting spherical magnetite nanoparticles. The shape of FMR spectra of both assemblies is shown to differ appreciably even at sufficiently large values of filling density of random clusters.