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Applications of magnetosomes synthesized by magnetotactic bacteria in medicine.

Alphandéry E - Front Bioeng Biotechnol (2014)

Bottom Line: Different methods that can be used to prepare the magnetosomes for these applications are described.The toxicity and biodistribution results that have been published are summarized.The advantageous properties of the magnetosomes compared with those of chemically synthesized nanoparticles of similar composition are also highlighted.

View Article: PubMed Central - PubMed

Affiliation: Nanobacterie SARL , Paris , France † ; Institut de Minéralogie et de Physique des Milieux Condensés, Université Pierre et Marie Curie , Paris , France.

ABSTRACT
Magnetotactic bacteria belong to a group of bacteria that synthesize iron oxide nanoparticles covered by biological material that are called magnetosomes. These bacteria use the magnetosomes as a compass to navigate in the direction of the earth's magnetic field. This compass helps the bacteria to find the optimum conditions for their growth and survival. Here, we review several medical applications of magnetosomes, such as those in magnetic resonance imaging (MRI), magnetic hyperthermia, and drug delivery. Different methods that can be used to prepare the magnetosomes for these applications are described. The toxicity and biodistribution results that have been published are summarized. They show that the magnetosomes can safely be used provided that they are prepared in specific conditions. The advantageous properties of the magnetosomes compared with those of chemically synthesized nanoparticles of similar composition are also highlighted.

No MeSH data available.


Related in: MedlinePlus

Transmission electron microscopy images of a single magnetotactic bacterium (A) of chains of magnetosomes extracted from whole magnetotactic bacteria (B) of individual magnetosomes detached from the chains by heat and SDS treatment (C).
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Figure 1: Transmission electron microscopy images of a single magnetotactic bacterium (A) of chains of magnetosomes extracted from whole magnetotactic bacteria (B) of individual magnetosomes detached from the chains by heat and SDS treatment (C).

Mentions: Depending on the type of application, different types of suspensions containing either magnetotactic bacteria or isolated magnetosomes can be prepared. For example, for targeting tumors, it has been suggested to use suspensions of living magnetotactic bacteria, which are administered intravenously and are naturally attracted by the anoxic environment of the tumor (Benoit et al., 2009). However, the use of living magnetotactic bacteria for medical applications will unlikely be accepted by regulatory agencies (FDA in the USA, EMA in Europe) and this review focuses on magnetosomes that will more likely be accepted for clinical trials. For treating cancers using magnetic hyperthermia, it has been suggested to use suspensions containing chains of magnetosomes (chains of magnetic nanoparticles) extracted from magnetotactic bacteria (Alphandéry et al., 2011a,b, 2012a, 2013). For other applications, the magnetosomes that have been used have been isolated from magnetotactic bacteria and treated to remove biological material surrounding them. They have then been coated with lipids for stabilization (Yoshino et al., 2007). To prepare suspensions containing living whole magnetotactic bacteria, AMB-1, MSR-1, or MS-1 strains can be purchased from the ATCC or DSMZ culture collection with a growth protocol, which is provided. A TEM (transmission electron microscopic) image of a typical whole magnetotactic bacterium containing several chains of magnetosomes is presented in Figure 1A. Among the different strains of magnetotactic bacteria, MSR-1 has achieved the highest yield of magnetosome production (170 mg/L/day) (Zhang et al., 2011), and therefore seems to be a promising strain for medical applications, which require a large quantity of magnetosomes. To obtain suspensions containing extracted chains of magnetosomes such as those shown in Figure 1B, the latter can be isolated from magnetotactic bacteria using either sonication (Taoka et al., 2006; Sun et al., 2008b; Alphandéry et al., 2011b), a treatment with sodium hydroxide (Philipse and Maas, 2002), with a French press (Grünberg et al., 2004; Matsunaga et al., 2007; Xiang et al., 2007), or with a pressure homogenizer (Guo et al., 2011; Tang et al., 2012). Different methods have also been suggested to purify the suspension of magnetosomes after extraction involving either magnetic separation of the magnetosomes from the cellular debris (Grünberg et al., 2001; Alphandéry et al., 2011b, 2012a), a treatment with proteinase K to remove surface proteins (Guo et al., 2011), phenylmethylsulfonyl fluoride to inhibit the activity of the protease, DNase I to remove DNA (Sun et al., 2007). The most commonly used method of sterilization for magnetosome suspensions is gamma rays (Guo et al., 2011). The magnetosomes can be stabilized in water. Before being administered to human, the suspensions of magnetosomes also need to be characterized. The biological material surrounding the magnetosomes can be characterized using chromatography, infrared spectroscopy, SDS Page, and mass spectroscopy (Grünberg et al., 2004). TEM can be used to measure the size of the magnetosomes and to verify the high level of crystallinity of the magnetosome core. Magnetic measurements could also be carried out to detect the Verwey transition, which would reveal the presence of magnetite in the magnetosomes (Alphandéry et al., 2008). Finally, it is also possible to obtain suspensions of individual magnetosomes isolated from magnetotactic bacteria (Figure 1C), in which most of the biological material has been removed by heating the suspensions of magnetosomes during 5 h at 90°C in the presence of 1% SDS (Alphandéry et al., 2011b, 2012a).


Applications of magnetosomes synthesized by magnetotactic bacteria in medicine.

Alphandéry E - Front Bioeng Biotechnol (2014)

Transmission electron microscopy images of a single magnetotactic bacterium (A) of chains of magnetosomes extracted from whole magnetotactic bacteria (B) of individual magnetosomes detached from the chains by heat and SDS treatment (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126476&req=5

Figure 1: Transmission electron microscopy images of a single magnetotactic bacterium (A) of chains of magnetosomes extracted from whole magnetotactic bacteria (B) of individual magnetosomes detached from the chains by heat and SDS treatment (C).
Mentions: Depending on the type of application, different types of suspensions containing either magnetotactic bacteria or isolated magnetosomes can be prepared. For example, for targeting tumors, it has been suggested to use suspensions of living magnetotactic bacteria, which are administered intravenously and are naturally attracted by the anoxic environment of the tumor (Benoit et al., 2009). However, the use of living magnetotactic bacteria for medical applications will unlikely be accepted by regulatory agencies (FDA in the USA, EMA in Europe) and this review focuses on magnetosomes that will more likely be accepted for clinical trials. For treating cancers using magnetic hyperthermia, it has been suggested to use suspensions containing chains of magnetosomes (chains of magnetic nanoparticles) extracted from magnetotactic bacteria (Alphandéry et al., 2011a,b, 2012a, 2013). For other applications, the magnetosomes that have been used have been isolated from magnetotactic bacteria and treated to remove biological material surrounding them. They have then been coated with lipids for stabilization (Yoshino et al., 2007). To prepare suspensions containing living whole magnetotactic bacteria, AMB-1, MSR-1, or MS-1 strains can be purchased from the ATCC or DSMZ culture collection with a growth protocol, which is provided. A TEM (transmission electron microscopic) image of a typical whole magnetotactic bacterium containing several chains of magnetosomes is presented in Figure 1A. Among the different strains of magnetotactic bacteria, MSR-1 has achieved the highest yield of magnetosome production (170 mg/L/day) (Zhang et al., 2011), and therefore seems to be a promising strain for medical applications, which require a large quantity of magnetosomes. To obtain suspensions containing extracted chains of magnetosomes such as those shown in Figure 1B, the latter can be isolated from magnetotactic bacteria using either sonication (Taoka et al., 2006; Sun et al., 2008b; Alphandéry et al., 2011b), a treatment with sodium hydroxide (Philipse and Maas, 2002), with a French press (Grünberg et al., 2004; Matsunaga et al., 2007; Xiang et al., 2007), or with a pressure homogenizer (Guo et al., 2011; Tang et al., 2012). Different methods have also been suggested to purify the suspension of magnetosomes after extraction involving either magnetic separation of the magnetosomes from the cellular debris (Grünberg et al., 2001; Alphandéry et al., 2011b, 2012a), a treatment with proteinase K to remove surface proteins (Guo et al., 2011), phenylmethylsulfonyl fluoride to inhibit the activity of the protease, DNase I to remove DNA (Sun et al., 2007). The most commonly used method of sterilization for magnetosome suspensions is gamma rays (Guo et al., 2011). The magnetosomes can be stabilized in water. Before being administered to human, the suspensions of magnetosomes also need to be characterized. The biological material surrounding the magnetosomes can be characterized using chromatography, infrared spectroscopy, SDS Page, and mass spectroscopy (Grünberg et al., 2004). TEM can be used to measure the size of the magnetosomes and to verify the high level of crystallinity of the magnetosome core. Magnetic measurements could also be carried out to detect the Verwey transition, which would reveal the presence of magnetite in the magnetosomes (Alphandéry et al., 2008). Finally, it is also possible to obtain suspensions of individual magnetosomes isolated from magnetotactic bacteria (Figure 1C), in which most of the biological material has been removed by heating the suspensions of magnetosomes during 5 h at 90°C in the presence of 1% SDS (Alphandéry et al., 2011b, 2012a).

Bottom Line: Different methods that can be used to prepare the magnetosomes for these applications are described.The toxicity and biodistribution results that have been published are summarized.The advantageous properties of the magnetosomes compared with those of chemically synthesized nanoparticles of similar composition are also highlighted.

View Article: PubMed Central - PubMed

Affiliation: Nanobacterie SARL , Paris , France † ; Institut de Minéralogie et de Physique des Milieux Condensés, Université Pierre et Marie Curie , Paris , France.

ABSTRACT
Magnetotactic bacteria belong to a group of bacteria that synthesize iron oxide nanoparticles covered by biological material that are called magnetosomes. These bacteria use the magnetosomes as a compass to navigate in the direction of the earth's magnetic field. This compass helps the bacteria to find the optimum conditions for their growth and survival. Here, we review several medical applications of magnetosomes, such as those in magnetic resonance imaging (MRI), magnetic hyperthermia, and drug delivery. Different methods that can be used to prepare the magnetosomes for these applications are described. The toxicity and biodistribution results that have been published are summarized. They show that the magnetosomes can safely be used provided that they are prepared in specific conditions. The advantageous properties of the magnetosomes compared with those of chemically synthesized nanoparticles of similar composition are also highlighted.

No MeSH data available.


Related in: MedlinePlus