174
M. L. Fdez-Gubieda et al.
relaxation time. Recently, Mériaux et al. [79] have demonstrated that magnetosomes
show an improved MRI contrasting perfomance as compared to commercially available SPIONs, attributed to the particles being monodomain and magnetically stable
at room temperature. Indeed, in vitro relaxometry measurements showed that magnetosomes of M. magneticum AMB-1 and Magnetovibrio blakemorei MV-1 display
a transverse relaxivity r 2 between three and four times higher than commercial SPIONs that leads to a significant gain in MRI sensitivity. The improved MRI contrasting
potential of MV-1 magnetosomes with respect to commercial SPIONs was demonstrated in in vivo tests aimed at visualizing mouse brain angiograms after systemic
injection. These experiments did also prove that a lower dose of iron was needed
when using magnetosomes as contrast agents instead of commercial SPIONs. As a
step forward, magnetosomes have been proposed as probes for molecular imaging.
Molecular imaging is a technique that combines MRI imaging with cell tracking
and/or molecular targeting via the functionalization of the magnetosome membrane.
A proper functionalization allows not only detecting with MRI where a tumour is
located in the body, but also the activity and expression of specific molecules. The feasibility of using magnetosomes as molecular imaging probes to target breast cancer
cells [80] and brain tumor in a mouse model of human glioblastoma [81] have been
recently demonstrated. In the latter work, magnetosomes of M. magneticum AMB1 were genetically modified so that their outer surface expressed the RGD peptide,
whose binding efficiency to α v β 3 integrin receptors overexpressed by tumor cells has
been largely demonstrated. In vivo MRI 11.2 T revealed the enhanced retention time
of the RGD-labelled magnetosomes within the tumor compared to the unlabelled
magnetosomes. The combined activity of magnetosomes as diagnosis and therapeutic agents (as molecular imaging probes and drug carriers/hyperthermia agents) has
also been proposed [63].
Given the potential of magnetosomes in biomedical applications, their biocompatibility must be addressed before they can be of clinical use, although a good
compatibility is expected due to the natural membrane surrounding the magnetic
cores, as preliminary in vitro and in vivo studies suggest [66, 82–85].
Although being magnetosomes the result of a genetically controlled biomineralization process assures their reproducibility and outstanding properties, the feasibility of tuning their magnetic properties could expand their potential applications.
In this sense, exposure of MTB to transition metal elements (Co, Mn, and Cu) has
been shown to change the magnetic properties of magnetosomes [62, 86–89]. In
particular, Co doping of magnetosomes from M. magneticum increases the magnetic
coercivity [88], which could improve the heating power of these magnetosomes
for hyperthermia applications. Doping of magnetosomes is generally achieved upon
addition of the doping element to the growth medium, but other routes involving
genetic modifications have been explored based on the expression of a metallophore
specific for Co and/or Ni in magnetospirilla [90].
Other biotechnological potential applications involve the use of MTB as biosorbents for trace radionuclides and heavy metals in environmental bioremediation [91].
MTB are being investigated in this field because unlike other microorganisms usable
M. L. Fdez-Gubieda et al.
relaxation time. Recently, Mériaux et al. [79] have demonstrated that magnetosomes
show an improved MRI contrasting perfomance as compared to commercially available SPIONs, attributed to the particles being monodomain and magnetically stable
at room temperature. Indeed, in vitro relaxometry measurements showed that magnetosomes of M. magneticum AMB-1 and Magnetovibrio blakemorei MV-1 display
a transverse relaxivity r 2 between three and four times higher than commercial SPIONs that leads to a significant gain in MRI sensitivity. The improved MRI contrasting
potential of MV-1 magnetosomes with respect to commercial SPIONs was demonstrated in in vivo tests aimed at visualizing mouse brain angiograms after systemic
injection. These experiments did also prove that a lower dose of iron was needed
when using magnetosomes as contrast agents instead of commercial SPIONs. As a
step forward, magnetosomes have been proposed as probes for molecular imaging.
Molecular imaging is a technique that combines MRI imaging with cell tracking
and/or molecular targeting via the functionalization of the magnetosome membrane.
A proper functionalization allows not only detecting with MRI where a tumour is
located in the body, but also the activity and expression of specific molecules. The feasibility of using magnetosomes as molecular imaging probes to target breast cancer
cells [80] and brain tumor in a mouse model of human glioblastoma [81] have been
recently demonstrated. In the latter work, magnetosomes of M. magneticum AMB1 were genetically modified so that their outer surface expressed the RGD peptide,
whose binding efficiency to α v β 3 integrin receptors overexpressed by tumor cells has
been largely demonstrated. In vivo MRI 11.2 T revealed the enhanced retention time
of the RGD-labelled magnetosomes within the tumor compared to the unlabelled
magnetosomes. The combined activity of magnetosomes as diagnosis and therapeutic agents (as molecular imaging probes and drug carriers/hyperthermia agents) has
also been proposed [63].
Given the potential of magnetosomes in biomedical applications, their biocompatibility must be addressed before they can be of clinical use, although a good
compatibility is expected due to the natural membrane surrounding the magnetic
cores, as preliminary in vitro and in vivo studies suggest [66, 82–85].
Although being magnetosomes the result of a genetically controlled biomineralization process assures their reproducibility and outstanding properties, the feasibility of tuning their magnetic properties could expand their potential applications.
In this sense, exposure of MTB to transition metal elements (Co, Mn, and Cu) has
been shown to change the magnetic properties of magnetosomes [62, 86–89]. In
particular, Co doping of magnetosomes from M. magneticum increases the magnetic
coercivity [88], which could improve the heating power of these magnetosomes
for hyperthermia applications. Doping of magnetosomes is generally achieved upon
addition of the doping element to the growth medium, but other routes involving
genetic modifications have been explored based on the expression of a metallophore
specific for Co and/or Ni in magnetospirilla [90].
Other biotechnological potential applications involve the use of MTB as biosorbents for trace radionuclides and heavy metals in environmental bioremediation [91].
MTB are being investigated in this field because unlike other microorganisms usable