Enhanced antitumor efficacy of biocompatible magnetosomes for the magnetic hyperthermia treatment of glioblastoma

Abstract

In this study, biologically synthesized iron oxide nanoparticles, called magnetosomes, are made fully biocompatible by removing potentially toxic organic bacterial residues such as endotoxins at magnetosome mineral core surfaces and by coating such surface with poly-L-lysine, leading to magnetosomes-poly-L-lysine (M-PLL). M-PLL antitumor efficacy is compared with that of chemically synthesized iron oxide nanoparticles (IONPs) currently used for magnetic hyperthermia. M-PLL and IONPs are tested for the treatment of glioblastoma, a dreadful cancer, in which intratumor nanoparticle administration is clinically relevant, using a mouse allograft model of murine glioma (GL-261 cell line). A magnetic hyperthermia treatment protocol is proposed, in which 25 µg in iron of nanoparticles per mm3 of tumor are administered and exposed to 11 to 15 magnetic sessions during which an alternating magnetic field of 198 kHz and 11 to 31 mT is applied for 30 minutes to attempt reaching temperatures of 43-46 °C. M-PLL are characterized by a larger specific absorption rate (SAR of 40 W/gFe compared to 26 W/gFe for IONPs as measured during the first magnetic session), a lower strength of the applied magnetic field required for reaching a target temperature of 43-46 °C (11 to 27 mT compared with 22 to 31 mT for IONPs), a lower number of mice re-administered (4 compared to 6 for IONPs), a longer residence time within tumours (5 days compared to 1 day for IONPs), and a less scattered distribution in the tumour. M-PLL lead to higher antitumor efficacy with full tumor disappearances achieved in 50% of mice compared to 20% for IONPs. This is ascribed to better ability of M-PLL, at equal iron concentrations, to maintain tumor temperatures at 43-46°C over a longer period of times.

Microbe‐Mediated Extracellular and Intracellular Mineralization: Environmental, Industrial, and Biotechnological Applications

“…Poly( l ‐lysine)‐coated magnetosomes have been used successfully for experimental magnetic hyperthermia treatment in a murine model of glioblastoma, an aggressive, fast‐growing brain tumor. [ 340 ] Similarly, magnetosomes extracted from Magnetospirillum gryphiswaldense MSR‐1 culture have been utilized, after purification, as theranostic agents in an in vivo murine subcutaneous model of colon carcinoma [ 341 ] as well as an in vivo murine xenograft model of glioblastoma. [ 342 ] Instead of using bioengineered harvested magnetosomes, a recent paper reported the use of live M .…”

Preparation and anti‐tumor efficiency evaluation of bacterial magnetosome–anti‐4‐1BB antibody complex: Bacterial magnetosome as antibody carriers isolated from Magnetospirillum gryphiswaldense

“…The distinctive characteristics of BMs suggested that they could be used as an effective vehicle, particularly as a potential magnetic carrier for drugs. BMs have been used as vehicles for antibodies, nucleic acids, and proteins in the laboratory . In our study, we developed a convenient way to conjugate antibodies to BMs.…”

“…Magnetosomes are small in size (40–120 nm) and are covered with a stable lipid membrane, which allows the magnetosomes to disperse very well . The bilayer membrane component of BMs contains many amino groups, which can be combined with biological molecules that include enzymes, antibodies, and antitumor medicines . Many in vitro results have demonstrated that BMs have many advantages over artificial iron oxide nanoparticles, particularly when the nanoparticles are used for biological applications .…”

A Method for Producing Highly Pure Magnetosomes in Large Quantity for Medical Applications Using Magnetospirillum gryphiswaldense MSR-1 Magnetotactic Bacteria Amplified in Minimal Growth Media

“…Using magnetotactism coupled to a system of oxygen detection (aerotactism), MTB then use their flagella to propel themselves toward the oxic-anoxic transition zone, where the oxygen concentration is optimal for their development and for magnetosome synthesis (Lefèvre and Bazylinski, 2013). Magnetosomes consist of magnetite minerals surrounded by a biological membrane (e.g., Faivre and Schüler, 2008;Le Fèvre et al, 2017;Arakaki et al, 2018). Using these bacteria, it has been possible to produce nanoparticles that fulfill most of the criteria mentioned above (Alphandéry, 2014).…”

“…In particular, MSR-1 magnetites display an organization in chains that prevents their aggregation (Heyen and Schüler, 2003), have high crystallinity, homogenous size distribution and improved heating properties in comparison to chemically synthesized IONP Mandawala et al, 2017). Hence, these biological nanoparticles have been considered for various medical applications, especially for tumor nanoparticle-mediated hyperthermia treatments (Alphandéry et al, 2017;Le Fèvre et al, 2017). Compared with other species, MSR-1 is the species that can reach the largest magnetosome production yield (MPY), making it the best candidate for producing magnetosomes for medical applications, as reported elsewhere by comparing the MPY obtained from the different MTB species, i.e., MSR-1, AMB-1, MS-1, MV-1 (Ali et al, 2017).…”