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International Journal of Nanomedicine 2020It is well known that when exposed to human blood plasma, nanoparticles are predominantly coated by a layer of proteins, forming a corona that will mediate the...
PURPOSE
It is well known that when exposed to human blood plasma, nanoparticles are predominantly coated by a layer of proteins, forming a corona that will mediate the subsequent cell interactions. Magnetosomes are protein-rich membrane nanoparticles which are synthesized by magnetic bacteria; these have gained a lot of attention owing to their unique magnetic and biochemical characteristics. Nevertheless, whether bacterial magnetosomes have a corona after interacting with the plasma, and how such a corona affects nanoparticle-cell interactions is yet to be elucidated. The aim of this study was to characterize corona formation around a bacterial magnetosome and to assess the functional consequences.
METHODS
Magnetosomes were isolated from the magnetotactic bacteria, (MSR-1). Size, morphology, and zeta potential were measured by transmission electron microscopy and dynamic light scattering. A quantitative characterization of plasma corona proteins was performed using LC-MS/MS. Protein absorption was further examined by circular dichroism and the effect of the corona on cellular uptake was investigated by microscopy and spectroscopy.
RESULTS
Various serum proteins were found to be selectively adsorbed on the surface of the bacterial magnetosomes following plasma exposure, forming a corona. Compared to the pristine magnetosomes, the acquired corona promoted efficient cellular uptake by human vascular endothelial cells. Using a protein-interaction prediction method, we identified cell surface receptors that could potentially associate with abundant corona components. Of these, one abundant corona protein, ApoE, may be responsible for internalization of the magnetosome-corona complex through LDL receptor-mediated internalization.
CONCLUSION
Our findings provide clues as to the physiological response to magnetosomes and also reveal the corona composition of this membrane-coated nanomaterial after exposure to blood plasma.
Topics: Adsorption; Blood Proteins; Cell Line; Endocytosis; Endothelial Cells; Humans; Magnetosomes; Magnetospirillum; Nanoparticles; Protein Corona
PubMed: 32189964
DOI: 10.2147/IJN.S220082 -
Frontiers in Microbiology 2014Magnetotactic bacteria (MTB) are considered the model species for the controlled biomineralization of magnetic Fe oxide (magnetite, Fe3O4) or Fe sulfide (greigite,... (Review)
Review
Magnetotactic bacteria (MTB) are considered the model species for the controlled biomineralization of magnetic Fe oxide (magnetite, Fe3O4) or Fe sulfide (greigite, Fe3S4) nanocrystals in living organisms. In MTB, magnetic minerals form as membrane-bound, single-magnetic domain crystals known as magnetosomes and the synthesis of magnetosomes by MTB is a highly controlled process at the genetic level. Magnetosome crystals reveal highest purity and highest quality magnetic properties and are therefore increasingly sought after as novel nanoparticulate biomaterials for industrial and medical applications. In addition, "magnetofossils," have been used as both past terrestrial and potential Martian life biosignature. However, until recently, the general belief was that the morphology of mature magnetite crystals formed by MTB was largely unaffected by environmental conditions. Here we review a series of studies that showed how changes in environmental factors such as temperature, pH, external Fe concentration, external magnetic fields, static or dynamic fluid conditions, and nutrient availability or concentrations can all affect the biomineralization of magnetite magnetosomes in MTB. The resulting variations in magnetic nanocrystals characteristics can have consequence both for their commercial value but also for their use as indicators for ancient life. In this paper we will review the recent findings regarding the influence of variable chemical and physical environmental control factors on the synthesis of magnetosome by MTB, and address the role of MTB in the global biogeochemical cycling of iron.
PubMed: 24575087
DOI: 10.3389/fmicb.2014.00049 -
Chemical Science Sep 2016Living organisms often exploit solid but poorly ordered mineral phases as precursors in the biomineralization of their inorganic body parts. Generally speaking, such... (Review)
Review
Living organisms often exploit solid but poorly ordered mineral phases as precursors in the biomineralization of their inorganic body parts. Generally speaking, such precursor-based approaches allow the organisms - without the need of high supersaturation levels - to accumulate significant quantities of mineral material at the desired place and time, where they can be molded and crystallized into the right morphology and structure. This strategy is also of interest in the field of bioinspired materials science, as it potentially enables the bottom-up creation of novel materials with equal or improved functionality as compared to Nature, in water and at ambient temperatures. Also for the biomineralization of magnetite (FeO) such a strategy has been reported: ferrihydrite, a poorly crystalline iron oxide, has been identified as a precursor for the final magnetite phase in the magnetosomes of magnetotactic bacteria as well as in the outer layers of chiton teeth. In this perspective, we discuss the efforts of us and others to understand and tune the nucleation and growth of magnetite crystals to date, in aqueous, room-temperature syntheses and employing different solid precursor phases. The various examples demonstrate the importance of the precursor approach in controlling the different properties of magnetite nanoparticles.
PubMed: 30034699
DOI: 10.1039/c6sc00523c -
Pharmaceutics Jan 2023Targeted nanoparticles of different origins are considered as new-generation diagnostic and therapeutic tools. However, there are no targeted drug formulations within... (Review)
Review
Targeted nanoparticles of different origins are considered as new-generation diagnostic and therapeutic tools. However, there are no targeted drug formulations within the composition of nanoparticles approved by the FDA for use in the clinic, which is associated with the insufficient effectiveness of the developed candidates, the difficulties of their biotechnological production, and inadequate batch-to-batch reproducibility. Targeted protein self-assembling nanoparticles circumvent this problem since proteins are encoded in DNA and the final protein product is produced in only one possible way. We believe that the combination of the endless biomedical potential of protein carriers as nanoparticles and the standardized protein purification protocols will make significant progress in "magic bullet" creation possible, bringing modern biomedicine to a new level. In this review, we are focused on the currently existing platforms for targeted self-assembling protein nanoparticles based on transferrin, lactoferrin, casein, lumazine synthase, albumin, ferritin, and encapsulin proteins, as well as on proteins from magnetosomes and virus-like particles. The applications of these self-assembling proteins for targeted delivery in vitro and in vivo are thoroughly discussed, including bioimaging applications and different therapeutic approaches, such as chemotherapy, gene delivery, and photodynamic and photothermal therapy. A critical assessment of these protein platforms' efficacy in biomedicine is provided and possible problems associated with their further development are described.
PubMed: 36678860
DOI: 10.3390/pharmaceutics15010231 -
Journal of Nanobiotechnology Dec 2019An 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...
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/g 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 mm 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/g down to ~ 29 nm and ~ 0 W/g. 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.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Cell Line, Tumor; Cell Survival; Female; Heating; Humans; Hyperthermia, Induced; Magnetic Fields; Magnetite Nanoparticles; Magnetosomes; Magnetospirillum; Mice; Mice, Nude; Particle Size; Theranostic Nanomedicine; Tissue Distribution
PubMed: 31870376
DOI: 10.1186/s12951-019-0555-2 -
Frontiers in Microbiology 2014Magnetosomes are membrane-enclosed magnetite nanocrystals synthesized by magnetotactic bacteria (MTB). They display chemical purity, narrow size ranges, and...
Magnetosomes are membrane-enclosed magnetite nanocrystals synthesized by magnetotactic bacteria (MTB). They display chemical purity, narrow size ranges, and species-specific crystal morphologies. Specific transmembrane proteins are sorted to the magnetosome membrane (MM). MamC is the most abundant MM protein of Magnetospirillum gryphiswaldense strain MSR-1. MamF is the second most abundant MM protein of MSR-1 and forms stable oligomers. We expressed staphylococcal protein A (SPA), an immunoglobulin-binding protein from the cell wall of Staphylococcus aureus, on MSR-1 magnetosomes by fusion with MamC or MamF. The resulting recombinant magnetosomes were capable of self-assembly with the Fc region of mammalian antibodies (Abs) and were therefore useful for functionalization of magnetosomes. Recombinant plasmids pBBR-mamC-spa and pBBR-mamF-spa were constructed by fusing spa (the gene that encodes SPA) with mamC and mamF, respectively. Recombinant magnetosomes with surface expression of SPA were generated by introduction of these fusion genes into wild-type MSR-1 or a mamF mutant strain. Studies with a Zeta Potential Analyzer showed that the recombinant magnetosomes had hydrated radii significantly smaller than those of WT magnetosomes and zeta potentials less than -30 mV, indicating that the magnetosome colloids were relatively stable. Observed conjugation efficiencies were as high as 71.24 μg Ab per mg recombinant magnetosomes, and the conjugated Abs retained most of their activity. Numbers of Vibrio parahaemolyticus (a common pathogenic bacterium in seafood) captured by recombinant magnetosome/Ab complexes were measured by real-time fluorescence-based quantitative PCR. One mg of complex was capable of capturing as many as 1.74 × 10(7) Vibrio cells. The surface expression system described here will be useful for design of functionalized magnetosomes from MSR-1 and other MTB.
PubMed: 24765089
DOI: 10.3389/fmicb.2014.00136 -
Contrast Media & Molecular Imaging 2018Magnetic fluid hyperthermia (MFH) with chemically synthesized nanoparticles is currently used in clinical trials as it destroys tumor cells with an extremely localized...
Magnetic fluid hyperthermia (MFH) with chemically synthesized nanoparticles is currently used in clinical trials as it destroys tumor cells with an extremely localized deposition of thermal energy. In this paper, we investigated an MFH protocol based on magnetic nanoparticles naturally produced by magnetotactic bacteria: magnetosomes. The efficacy of such protocol is tested in a xenograft model of glioblastoma. Mice receive a single intratumoral injection of magnetosomes, and they are exposed three times in a week to an alternating magnetic field with concurrent temperature measurements. MRI is used to visualize the nanoparticles and to monitor tumor size before and after the treatment. Statistically significant inhibition of the tumor growth is detected in subjects exposed to the alternating magnetic field compared to control groups. Moreover, thanks to magnetosomes high transversal relaxivity, their effective delivery to the tumor tissue is monitored by MRI. It is apparent that the efficacy of this protocol is limited by inhomogeneous delivery of magnetosomes to tumor tissue. These results suggest that naturally synthesized magnetosomes could be effectively considered as theranostic agent candidates for hyperthermia based on iron oxide nanoparticles.
Topics: Animals; Cell Line, Tumor; Disease Models, Animal; Glioblastoma; Magnetic Resonance Imaging; Magnetosomes; Magnetospirillum; Male; Mice, Nude; Temperature; Theranostic Nanomedicine; Tumor Burden
PubMed: 30116160
DOI: 10.1155/2018/2198703 -
Nanomaterials (Basel, Switzerland) May 2021Derived from magnetotactic bacteria (MTB), magnetosomes consist of magnetite crystals enclosed within a lipid bilayer membrane and are known to possess advantages over...
Derived from magnetotactic bacteria (MTB), magnetosomes consist of magnetite crystals enclosed within a lipid bilayer membrane and are known to possess advantages over artificially synthesized nanoparticles because of the narrow size distribution, uniform morphology, high purity and crystallinity, single magnetic domain, good biocompatibility, and easy surface modification. These unique properties have increasingly attracted researchers to apply bacterial magnetosomes (BMs) in the fields of biology and medicine as MRI imaging contrast agents. Due to the concern of biosafety, a long-term follow-up of the distribution and clearance of BMs after entering the body is necessary. In this study, we tracked changes of BMs in major organs of mice up to 135 days after intravenous injection using a combination of several techniques. We not only confirmed the liver as the well-known targeted organs of BMs, but also found that BMs accumulated in the spleen. Besides, two major elimination paths, as well as the approximate length of time for BMs to be cleared from the mice, were revealed. Together, the results not only confirm that BMs have high biocompatibility, but also provide a long-term in-vivo assessment which may further help to forward the clinical applications of BMs as an MRI contrast agent.
PubMed: 34067162
DOI: 10.3390/nano11051235 -
Journal of Nanobiotechnology Jan 2021Magnetic nanoparticles such as magnetosomes modified with antibodies allow a high probability of their interaction with targets of interest. Magnetosomes biomineralized...
BACKGROUND
Magnetic nanoparticles such as magnetosomes modified with antibodies allow a high probability of their interaction with targets of interest. Magnetosomes biomineralized by magnetotactic bacteria are in homogeneous nanoscale size and have crystallographic structure, and high thermal and colloidal stability. Camelidae derived nanobodies (Nbs) are small in size, thermal stable, highly water soluble, easy to produce, and fusible with magnetosomes. We aimed to functionalize Nb-magnetosomes for the analysis of the insecticide fipronil.
RESULTS
Three recombinant magnetotactic bacteria (CF, CF+ , and CFFF) biomineralizing magnetosomes with different abundance of Nbs displayed on the surface were constructed. Compared to magnetosomes from the wild type Magnetospirillum gryphiswaldense MSR-1, all of the Nb-magnetosomes biosynthesized by strains CF, CF+ , and CFFF showed a detectable level of binding capability to fipronil-horseradish peroxidase (H2-HRP), but none of them recognized free fipronil. The Nb-magnetosomes from CFFF were oxidized with HO or a glutathione mixture consisting of reduced glutathione and oxidized glutathione in vitro and their binding affinity to H2-HRP was decreased, whereas that to free fipronil was enhanced. The magnetosomes treated with the glutathione mixture were employed to develop an enzyme-linked immunosorbent assay for the detection of fipronil in water samples, with average recoveries in a range of 78-101%.
CONCLUSIONS
The economical and environmental-friendly Nb-magnetosomes biomineralized by the bacterial strain MSR-1 can be potentially applied to nanobody-based immunoassays for the detection of fipronil or nanobody-based assays in general.
Topics: Bacillus subtilis; Bacterial Proteins; Batch Cell Culture Techniques; Fermentation; Glutathione; Hydrogen Peroxide; Immunoassay; Insecticides; Magnetosomes; Magnetospirillum; Pyrazoles; Single-Chain Antibodies; Single-Domain Antibodies
PubMed: 33468141
DOI: 10.1186/s12951-021-00773-z -
PloS One 2012Magnetospirillum gryphiswaldense strain MSR-1 has the unique capability of taking up large amounts of iron and synthesizing magnetosomes (intracellular magnetic...
Magnetospirillum gryphiswaldense strain MSR-1 has the unique capability of taking up large amounts of iron and synthesizing magnetosomes (intracellular magnetic particles composed of Fe(3)O(4)). The unusual high iron content of MSR-1 makes it a useful model for studying biological mechanisms of iron uptake and homeostasis. The ferric uptake regulator (Fur) protein plays a key role in maintaining iron homeostasis in many bacteria. We identified and characterized a fur-homologous gene (MGR_1314) in MSR-1. MGR_1314 was able to complement a fur mutant of E. coli in iron-responsive manner in vivo. We constructed a fur mutant strain of MSR-1. In comparison to wild-type MSR-1, the mutant strain had lower magnetosome formation, and was more sensitive to hydrogen peroxide and streptonigrin, indicating higher intracellular free iron content. Quantitative real-time RT-PCR and chromatin immunoprecipitation analyses indicated that Fur protein directly regulates expression of several key genes involved in iron transport and oxygen metabolism, in addition it also functions in magnetosome formation in M. gryphiswaldense.
Topics: Bacterial Proteins; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Genes, Bacterial; Hydrogen Peroxide; Iron; Magnetosomes; Magnetospirillum; Metabolic Networks and Pathways; Oxygen; Promoter Regions, Genetic; Protein Binding; Repressor Proteins
PubMed: 22238623
DOI: 10.1371/journal.pone.0029572