Magnetosomes and Magnetosome Mimics: Preparation, Cancer Cell Uptake and Functionalization for Future Cancer Therapies

Abstract

Magnetic magnetite nanoparticles (MNP) are heralded as model vehicles for nanomedicine, particularly cancer therapeutics. However, there are many methods of synthesizing different sized and coated MNP, which may affect their performance as nanomedicines. Magnetosomes are naturally occurring, lipid-coated MNP that exhibit exceptional hyperthermic heating, but their properties, cancer cell uptake and toxicity have yet to be compared to other MNP. Magnetosomes can be mimicked by coating MNP in either amphiphilic oleic acid or silica. In this study, magnetosomes are directly compared to control MNP, biomimetic oleic acid and silica coated MNP of varying sizes. MNP are characterized and compared with respect to size, magnetism, and surface properties. Small (8 ± 1.6 nm) and larger (32 ± 9.9 nm) MNP are produced by two different methods and coated with either silica or oleic acid, increasing the size and the size dispersity of the MNP. The coated larger MNP are comparable in size (49 ± 12.5 nm and 61 ± 18.2 nm) to magnetosomes (46 ± 11.8 nm) making good magnetosome mimics. All MNP are assessed and compared for cancer cell uptake in MDA-MB-231 cells and importantly, all are readily taken up with minimal toxic effect. Silica coated MNP show the most uptake with greater than 60% cell uptake at the highest concentration, and magnetosomes showing the least with less than 40% at the highest concentration, while size does not have a significant effect on uptake. Finally, surface functionalization is demonstrated for magnetosomes and silica coated MNP using biotinylation and EDC-NHS, respectively, to conjugate fluorescent probes. The modified particles are visualized in MDA-MB-231 cells and demonstrate how both naturally biosynthesized magnetosomes and biomimetic silica coated MNP can be functionalized and readily up taken by cancer cells for realization as nanomedical vehicles.

Assessing Cytotoxicity, Endotoxicity, and Blood Compatibility of Nanoscale Iron Oxide Magnetosomes for Biomedical Applications

“…Therefore, strategies must be developed to reduce endotoxin-induced pyrogenicity as much as possible, also because this represents a prerequisite for GMP-compliant production and clinical approval in the future. By overcoming endotoxin-related biocompatibility issues, magnetosomes can likely be developed into a versatile theranostic tool. , In contrast to chemically synthesized nanoparticles, magnetosomes can be genetically engineered in a selective and highly controllable manner, enabling the display of functional moieties on the particle surface. , Thus, besides their usage as drug carriers, ,, magnetosomes might be equipped with specific targeting peptides, , allowing not only the specific recognition but also the efficient treatment of (circulating) tumor cells as a flexible nanoparticle agent. , …”

Biomimetic Nanomaterials: Diversity, Technology, and Biomedical Applications

“…In this case, magnetosomes are isolated from MTB cells and subjected to purification, followed by biotinylation or encapsulation in an inorganic shell. Such magnetic NPs can be used for contrast enhancement in magnetic resonance imaging, magnetic particle imaging, and magnetic hyperthermia [ 44 , 89 ].…”

“…Methods of the second group, from our point of view, were more promising due to the ability to create a material structure similar to natural analogues at the level of individual atoms. They included the biosynthesis of magnetic NPs from oxygen-free solutions containing recombinant MamC in anaerobic conditions [ 32 , 48 , 85 , 86 , 87 ], magnetite biomineralization using PEGylated human ferritin NPs [ 52 ], and the silica encapsulation or biotinylation of isolated bacterial magnetosomes [ 44 , 89 ]. Thus, the methods of the second group made it possible to achieve a combination of the advantages of biogenic magnetic NPs (magnetosomes) and their synthetic counterparts, minimizing the disadvantages of both.…”

Biosensors and Drug Delivery in Oncotheranostics Using Inorganic Synthetic and Biogenic Magnetic Nanoparticles

“…The experiments demonstrated the uptake of particles by MDA-MB-231 cells through inclusion bodies and those particles were located intracellularly. The authors consider that due to the size of the particles, intracellular uptake most likely occurred via pinocytosis with the inclusion bodies being pinosomes or lysosomes, although other processes of MNP internalization including clathrin-mediated endocytosis, etc., are also possible [ 239 ]. The particle size was shown to have a negligible effect on overall iron uptake by the MDA-MB-231 cell line.…”