REVIEW

Magnetotactic bacteria for cancer therapy

Abhilasha S. Mathuriya

Received: 5 August 2014 / Accepted: 6 November 2014

� Springer Science+Business Media Dordrecht 2014

Abstract Cancer is characterized by anomalous cell

growth. Conventional therapies face many challenges

and hence alternative treatment methods are in great

demand. In addition, nature offers the best inspiration

and recently many therapies of natural origin have

proved multi-targeted, multi-staged, and a multi-

component mode of action against cancer. Magneto-

tactic bacteria and magnetosomes-based treatment

methods are among them. Present paper reviews

various routes by which magnetotactic bacteria and

magnetosomes contribute to cancer therapy.

Keywords Bacteria and cancer � Drug delivery �Hyperthermia � Magnetotactic bacteria �Magnetosomes

Introduction

Cancer is characterized by anomalous and invasive

cell growth. A cancer becomes incurable when it

spreads to other parts of the body in a process called

metastasis. Many conventional anti-cancer therapies,

viz. surgical, radio- and chemotherapy, are available

to cure or stop cancer growth (Patyar et al. 2010). One

of the major lacunas in these therapies is the gener-

ation of resistance that creates a need for alternative

therapies. Many other alternate therapies, viz. gene

therapy, dichloroacetate therapy, complementary ther-

apy, insulin-potentiating therapy and bacterial treat-

ment (Jain 2001), are also available. All these

therapies have their inherent potentials and side-

effects. There is a need for more effective cancer

treatments with fewer side effects. Recently nano-

technology has opened many doors in cancer therapy.

Magnetotactic bacteria (MTB) and their magneto-

somes are among those solutions which offer great

promise in cancer therapy in various ways.

MTB are ubiquitous, aquatic and motile bacteria

that mineralize magnetosome—a forte organelle with

nano-sized magnetic magnetite (Fe3O4) or greigite

(Fe3S4) crystals in various arrangements (Arakaki

et al. 2008). These crystals are enclosed by a

membrane containing phospholipids, phosphatidyl

ethanolmine, phosphatidyl glycerol, some amino

groups and specific proteins. This membrane controls

the crystal size and morphology and generates a matrix

for the function and stability of magnetosomes and

therefore, magnetosomes can act as biogenic material

with high bio- and nano-technological potential (Ara-

kaki et al. 2008).

MTB (the entire living cell) and magnetosomes

both offer applications in various areas of cancer

treatment (Yoshino et al. 2010) in different ways

(Fig. 1). Although commercially-available iron oxide

particles are produced via chemical synthesis, yet they

A. S. Mathuriya (&)

Department of Biotechnology, Anand Engineering

College, NH-2, Keetham, Agra 282007, India

e-mail: imabhilasha@gmail.com

123

Biotechnol Lett

DOI 10.1007/s10529-014-1728-6

cannot compete with magnetosomes in terms of their

intrinsic magnetic features, genetically-controlled

uniform nano-morphology, narrow size distributions,

having a biomembrane envelope (Arakaki et al. 2008;

Yoshino et al. 2010; Hofer 2013; Alphandery 2014).

This review is an attempt to summarize the applica-

bility of the MTB and magnetosomes in the various

areas of cancer treatment.

Drug delivery systems

Chemotherapy is an effective therapy against active

cancer cells using anti-cancer drugs, singly or in

combination. However, it leads to damage healthy

cells, such as blood and hair cells. As anti-cancer drug

administration inhibits or stops cell growth, the

concentrations of the drug should be below a toxic

level and above a level of minimal therapeutic effect.

Unfortunately, the human body does not have the

ability to segregate these spatio-targeted profiles and

therefore drugs distribute throughout the body and can

affect healthy organs which do not require drug

treatment. In addition, the body’s defence mechanism

generally excretes foreign substances (Kingsley et al.

2006). To meet these challenges, many research

groups have investigated drug delivery systems that

use more biocompatible and biodegradable materials

to control the drug release from microstructures to

reduce the side-effects (Sahoo and Labhasetwar 2003;

Sinha et al. 2006; Suri et al. 2007). The concept of such

an efficient system is to locate drugs at the targeted

site, and at the required concentration for the right

period of time (Kingsley et al. 2006).

Recently, MTB and magnetosomes have proved

their candidature (Schuler and Frankel 1999; Hopkin

2004; Martel 2006, 2014; Munoz-Jimenez et al. 2010)

as smart drug carriers due to their unique

Fig. 1 Application of magnetotactic bacteria and magnetosomes in cancer therapy

Biotechnol Lett

123

characteristics such as para-magnetism, uniform nano

size, narrow size distribution and being membrane

bound (Gorby et al. 1988; Nakamura et al. 1991;

Bazylinski et al. 1994; Hoell et al. 2004; Grunberg

et al. 2004). Magnetosomes contain amino groups and

glycerol on their membrane surface, which allows

them to be coupled to another ligand. Therefore,

magnetosomes can act as efficient drug carriers with a

higher drug loading ratio than some artificial magnetic

particles. Magnetoliposomes, containing cis-dia-

mmine-dichloro-platinum(II) (cisplatin: platinum-

containing anti-cancer drug) coupled with magneto-

somes, have been evaluated for drug targeting and

controlled release at tumor sites (Matsunaga et al.

1997). The capture volume of the magnetoliposomes

was 1.7 times higher than that of artificial magnetic

particles. In addition, magnetoliposomes released

their content over 2 h on application of a rotating

magnetic field (Matsunaga et al. 1997). In another

study (Deng et al. 2013), cytosine arabinoside (Ara-C)

was combined with magnetosomes via cross-linking

with genipin. The results exhibited about 90 %

encapsulation efficiency and 47 % drug loading

efficiency, for 72 h. The Ara-C system showed a

long-term stability, and 80 % of the drugs could be

released over 3 months without an initial burst.

Accurate drug delivery to target organs is a critical

need for a successful, cell-based therapy by stem cells

or immune cells. Contrast-agent labelling before

implantation can be a powerful tool for observing

cellular actions by MRI. Schwarz et al. (2009)

investigated magnetosomes uptake into dendritic cells

and hematopoietic Flt3? stem cells from the bone

marrow of mouse and observed that uptake of

magnetosomes into the cells increased magnetic

activity; cells loaded with magnetosomes were

promptly detected by MRI.

Radiotherapy is the application of radiations, viz.

gamma rays, X-rays, electron beam to weaken or stop

cancer cell from further growth and multiplication

(Kumar et al. 2009). Magnetosomes could also be

coupled to radioactive isotopes, e.g. using chelates,

radioactive-labelled molecules, such as nucleic acids

and proteins (Sun et al. 2011), and would offer a better

internal radiation of solid tumors because of their

accurate targeted delivery (Sun et al. 2011). Further,

(Sun 2007; Sun et al. 2008) doxorubicin was loaded

onto bacterial magnetosomes (DBMs) in EMT-6 and

HL60 cell-lines to study in vitro and in vivo anti-

neoplastic effects on hepatic cancer. DBMs showed a

slower doxorubicin release into serum and maintained

80 % stability up to 48 h of incubation. Liu et al.

(2013), loaded methotrexate and genipin onto mag-

netosomes with about 50 % drug loading, up to 98 %

encapsulation efficiency and stable drug release.

G protein-coupled receptors (GPCRs) expression

G protein-coupled receptors (GPCRs) are the largest

family of membrane proteins in the human genome.

They have applications in drug discovery, cancer

treatment, endocrine, neural and other disorders

(Katritch and Abagyan 2011). GPCRs contain many

hydrophobic domains which cause complexities in the

purification of GPCRs from cells and in the loss of

native conformation. The GPCR with natural confor-

mation was manufactured by expression of the GPCR

gene in MTB (Matsunaga et al. 2004). The GPCR gene

was expressed as a chimeric gene coding for the GPCR

and anchor protein which was selected from magnetite

particle membrane proteins of their fragments. Yosh-

ino et al. (2002) used D1R as a model GPCRs and

fused it to magnetosomes-membrane-specific-protein

Mms16. Further, GPCRs were also assembled into the

lipid membrane of magnetosomes of M. magneticum

AMB-1 (Yoshino et al. 2004).

Single nucleotide polymorphisms (SNPs)

SNPs are human genetic polymorphisms that help in

the identification of genes associated with diseases

such as cancer, and diabetes (Tomita-Mitchell et al.

1998). To produce accurate data, SNP analysis

requires large sample, therefore high-throughput and

accurate multiple-assay system is required for SNP

analysis (Tomita-Mitchell et al. 1998). Maruyama

et al. (2004) developed a protocol based on DNA

thermal dissociation curve analysis for an automated

system with magnetosomes by developing a new

method for avoiding light scattering caused by nano-

meter-size particles when using commercially-avail-

able fluorescent dyes such as FITC, Cy3, and Cy5 for

labeling chromophores. SNPs of aldehyde dehydro-

genase-2 (Maruyama et al. 2004), epidermal growth

factor receptor (Maruyama 2007) and transforming

growth factor b-1 (Ota et al. 2003; Matsunaga et al.

Biotechnol Lett

123

2007) genes have been detected. In another study, a

semi-automated SNPs detection system, based on

thermal-dissociation-curve-analysis and allele-spe-

cific oligonucleotide hybridization using magneto-

somes was developed by Matsunaga et al. (2007).

Magnetic fluid hyperthermia

Hyperthermia treatment of tumors is one of the most

promising biomedical applications for the treatment of

some causes. In this treatment, heat-sensitive tumor

cells are destroyed by high temperatures (Hergt et al.

2006). Hyperthermia is applied in conjugation with

other methodologies such as radiotherapy and chemo-

therapy. Hyperthermia facilitates increased oxygena-

tion and perfusion of neoplastic hypoxic cells which

leads to increased absorption of chemotherapeutic

drugs (Dutz and Hergt 2013). Microwave hyperther-

mia cancer treatment in conjunction with radiation,

has been approved by Food and Drug Administration

(Luk et al. 1986). Non selective heating by chemical

metal nano particles (MNP), cause damage to sur-

rounding healthy tissue and pose severe side effects.

Therefore, there is a need for significantly improved

and more selective hyperthermia agents and proce-

dures for uniformly controlled induction heating, and

prevention of the necrosis of normal tissue (Alphan-

dery et al. 2013). An important characteristic of

magnetosomes is their ability to generate heat on

application of an oscillating magnetic field. This

feature conceives the idea that these magnetosomes

might be applicable in the destruction or inactivation

of tumor cells through hyperthermia or thermoablation

(Alphandery et al. 2011a).

Alphandery et al. (2011a) reported the heating

efficiency and magnetic properties of cobalt-doped

magnetosomes for applications in hyperthermia-

based, magnetic field cancer therapy. The hysteresis

losses, magnetic properties and heating efficiency of

the magnetosome chains were enhanced after cobalt

doping. Further hyperthermia treatment of mouse

tumor by magnetosomes by applying an alternative

magnetic field was also described (Alphandery et al.

2011b). In addition, Alphandery et al. (2011c) studied

the heat production capabilities of MTB cells,

extracted chains of magnetosomes, and extracted

individual magnetosomes without membranes, when

exposed to an oscillating magnetic field. The specific

heat absorption rates of all of those samples were

higher than that of super-paramagnetic nanoparticles.

Further, MDA-MB-231 breast cancer cells incubated

with magnetosomes with a 183 kHz frequency alter-

native magnetic field with field strengths of 20, 40, or

60 mT, were almost completely destroyed (Alphan-

dery et al. 2011d). Some research groups (Liu et al.

2012; Alphandery et al. 2012) are applying magneto-

somes in magnetic fluid hyperthermia in different

ways.

Magnetic resonance imaging (MRI)

MRI is a technique that demonstrates non-invasive

molecular imaging of cells and cellular activities. It

can monitor cellular processes such as cancer growth

and metastasis (Goldhawk et al. 2012). The MRI

approach is favoured as it: (a) provides non-invasive

details, (b) allows simultaneous tracking and actuation

of the nanoparticles, (c) provides very specific local-

ization of the magnetic particles, and (d) is readily

available at most hospitals. In MRI, cell tracking

methods involve exogenous labels, like super-para-

magnetic iron-oxide nanoparticles, that however, are

degraded by the cellular activities like mitosis and

therefore lack an inherent biological function (Gold-

hawk et al. 2012).

Magnetosomes can also be used as MR contrast

agents for cell tracking and imaging as they can

differentiate between healthy and pathological tissues.

Herborn et al. (2003) characterized magnetosomes as

super-paramagnetic contrast agents for MRI and their

longitudinal and transverse relaxivities were calcu-

lated to be 7.688 and 147.67 mmol-1 s-1. Lisy et al.

(2007) assessed the use of fluorochrome-coupled

magnetosomes (FCM) as bimodal contrast agent for

both MRI and near-infrared fluorescence optical

imaging of cultured macrophages. FCM showed

higher fluorescence intensities above 670 nm. Further,

macrophages could also be labelled with FCM and

were imaged using both a 1.5 T MR scanner and near-

infrared fluorescence imaging. Felfoul et al. (2007)

studied application of MTB as bio-carriers for drug

delivery, and observed that the magnetosomes in MTB

could track bacterial displacement in vivo using MRI.

In another study, the in vitro and in vivo ability of M.

magneticum AMB-1 as MRI contrast was determined

(Benoit et al. 2009): AMB-1 could produce positive

Biotechnol Lett

123

MRI contrast and colonize mouse tumor xenografts.

Felfoul et al. (2010) observed that magnetosomes were

predominant sources of contrast in MRI. Goldhawk

et al. (2012) reviewed the magnetosomes as reporters

of gene expression in MRI and found their suitability

and superiority. Vereda et al. (2009) also reported the

application of magnetosomes as MRI contrast agent.

In their patent application, Gambhir et al. (2010)

disclosed the use of M. magneticum AMB-1 as an MRI

contrast agent and a method of tumor detection using

MTB enhancement for the positive contrast of MRI.

Afkhami et al. (2011) developed a method for MTB

encapsulation by magnetic resonance navigation in a

controlled release pattern and its carriage towards the

capillary network area where they could released and

guided towards the tumor.

Robotics or actuators

The microrobot construction within the 1–2 lm range

using only artificial components is difficult due to

several technological obstructions. Therefore, there is a

need to find a biological entity having an embedded

power and propulsion system. Technically, MTB can

act like micro-robots as they possess an efficient

molecular motor, sensory and actuation capabilities as

well as an embedded remote control interface (Martel

2012). Motile MTBs having flagella are responsible for

the actuation and propulsion. They can therefore propel

and steer micro-devices, and nanorobots under com-

puter control. For an example, MC-1 MTBs propelled

themselves with flagella generating a thrust exceeding

4 pN (Lu and Martel 2006). If this ability could be

coupled with appropriate computer-controlled mag-

netic fields of a few Gausses, it can perform tasks on

nanometric scale (Lu and Martel 2006).

Martel et al. (2009) described several medical

robots that performed efficiently through suitable

software/hardware subsystems in the microvascula-

ture modules. This methodology allowed higher

targeting efficacy and operations in locations as

tumoral lesions which were accessible only through

complex microvasculature networks. Mokrani et al.

(2010) studied the ability of MTBs to penetrate 3D

multi-cellular tumor spheroids. This model showed

that MTB could be navigated in tumor environments

and act as a microrobot for drug delivery under

computer magnetic field.

Magnetic resonance targeting (MRT) is among

latest technologies in medical robotics that facilitates

enhanced target interventions in the human body. It

uses MRI to receive tracking data and to determine the

position of entities and guide them towards a specific

location in the body through the vascular network.

Microrobotic navigable entities for MRT were studied

by Martel (2010) to target colorectal tumors by

controllable MTBs having propelling thrust force by

two flagella exceeding 4 pN, i.e. a tenfold increase

over typical flagellated bacteria. Felfoul et al. (2011)

reported computer-controlled MTB navigation

towards solid tumors with 300 lm s-1 swimming

velocities, without an external power source. Khalil

et al. (2013a) studied closed-loop control strategy for

MTBs-based microrobots. Khalil et al. (2013b) also

demonstrated that this control system positioned an

MTB at an average velocity of 28 lm s-1, within an

average region-of-convergence of 40 lm.

Perspectives

Although MTBs and magnetosomes can help in cancer

treatment in different ways, they are still rarely

employed in vivo as drug carriers. This is due to their

uncertain biocompatibility and pharmacokinetics.

Magnetosomes can be considered biocompatible due

to: (i) their biological origin (Xiang et al. 2007), (ii)

negligible chemical toxicity (Hafeli and Pauer 1999;

Wagner et al. 2006), and (iii) insolubility of Fe3O4.

Magnetosomes are enclosed by a lipid bilayer and

specific soluble and trans-membrane proteins helps

magnetosomes to attain biocompatibility. On the other

hand, toxic properties of magnetosomes might be due

to: (i) their nano-scale size, which leads to deposition

and aggregation of nanoparticles in the body (Sun

et al. 2010), (ii) impurities (particularly proteins,

nucleic acids, and polysaccharides) associated with

magnetosomes during extraction from cells, and their

immunotoxicity, and (iii) membrane-containing pro-

teins (Jevprasesphant et al. 2003; Grunberg et al.

2004).

Many scientists have studied in vivo and in vitro

biocompatibility of magnetosomes in target cells (Xiang

et al. 2007; Sun 2009; Liu et al. 2012; Taherkhani et al.

2014). Xiang et al. (2007) evaluated in vitro cytotoxicity

of magnetosomes for mouse fibroblasts and observed

that magnetosomes were not toxic. A target distribution

Biotechnol Lett

123

of magnetosomes in the sublingual vena of Sprague-

Dawley rats was observed by Sun (2009) and the

distributions of magnetosomes in dejecta (liquid or solid

waste matter, shed or discharged from the body), serum,

urine and in other main organs were examined. After

injection, the presence of magnetosomes was observed

only in the liver and no evidence of the magnetosome

existence was observed in the dejecta and urine during

72 h after intravenous administration. In addition,

histological examination of major organs of rats showed

no remarkable pathological changes except thicker

interlobular septa in lungs and increased number of

vacuoles in livers (Sun 2009). In another study,

hemolysis assay, MTT test, and micronucleus test were

conducted by Yan (2012). Magnetosomes up to

4 mg ml-1 showed no cytotoxic, genotoxic, and hemo-

lytic effects, claiming good biocompatibility. Cytotox-

icity studies on human breast cancer cells MCF-7 were

conducted by Liu et al. (2012) and, although cell

viability was decreased by the heat derived from

magnetosomes, lower toxicities under an alternative

magnetic field was observed. Taherkhani et al. (2014)

observed that liposomal attachments to MTB formula-

tion improved the biocompatibility of MTB, whereas

attachment does not interfere with liposomal uptake.

The lack of international guidelines to evaluate the

toxicity of nanomaterials (Malloy 2011) is responsible

for the lag in commercialization of MNPs-based

products and processes. Additionally, the production

of MTBs must comply with the industrial and

healthcare requirements. If these lacunas are over-

come, MTBs and magnetosomes will certainly play an

important role in cancer therapy in the near future due

to their superior analytical performance, novel char-

acteristic features, and a plethora of applications.

Acknowledgment Author acknowledges Mr. Anshul Kumar

for editing this manuscript.

References

Afkhami F, Taherkhani S, Mohammadi M, Martel S (2011)

Encapsulation of magnetotactic bacteria for targeted and

controlled delivery of anticancer agents for tumor therapy.

Conf Proc IEEE Eng Med Biol Soc 2011:6668–6671

Alphandery E (2014) Applications of magnetosomes synthe-

sized by magnetotactic bacteria in medicine. Front Bioeng

Biotechnol 2:5

Alphandery E, Carvallo C, Menguy N, Chebbi I (2011a) Chains

of cobalt doped magnetosomes extracted from AMB-1

magnetotactic bacteria for application in alternative mag-

netic field cancer therapy. J Phy Chem C 115:11920–11924

Alphandery E, Faure S, Raison L, Duguet EM, Howse PA,

Bazylinski DA (2011b) Heat production by bacterial

magnetosomes exposed to an oscillating magnetic field.

J Phys Chem C 115:18–22

Alphandery E, Faure S, Chebbi I (2011b) US Patent, WO

2011,061259 A1. Treatment of cancer or tumor induced by

the release of heat generated by various chains of mag-

netosomes extracted from magnetotactic bacteria and

submitted to an alternative magnetic field

Alphandery E, Faure S, Seksek O, Guyot F, Chebbi I (2011d)

Chains of magnetosomes extracted from AMB-1 mag-

netotactic bacteria for application in alternative magnetic

field cancer therapy. ACS Nano 5:6279–6296

Alphandery E, Guyot F, Chebbi I (2012) Preparation of chains

of magnetosomes, isolated from Magnetospirillum mag-

neticum strain AMB-1 magnetotactic bacteria, yielding

efficient treatment of tumors using magnetic hyperthermia.

Int J Pharm 434:444–452

Alphandery E, Chebbi I, Guyot F, Dubief MD (2013) Use of

bacterial magnetosomes in the magnetic hyperthermia

treatment of tumours: a review. Int J Hyperthermia

29:801–809

Arakaki A, Nakazawa H, Nemoto M, Mori T, Matsunaga T

(2008) Formation of magnetite by bacteria and its appli-

cation. J R Soc Interface 5:977–999

Bazylinski DA, Garratt-Reed A, Frankel RB (1994) Electron

microscopic studies of magnetosomes in magnetotactic

bacteria. Microsc Res Tech 27:389–401

Benoit MR, Mayer D, Barak Y, Chen IY, Hu W, Cheng Z, Wang

SX, Spielman DM, Gambhir SS, Matin A (2009) Visual-

izing implanted tumors in mice with magnetic resonance

imaging using magnetotactic bacteria. Clin Cancer Res

15:5170–5177

Chen Y, Kosmas P, Martel S (2013) Microwave breast tumor

detection and size estimation using contrast-agent-loaded

magnetotactic bacteria. Int Conf Proc Eng Med Biol Soc

5481–5484

Deng Q, Liu Y, Wang S, Xie M, Wu S, Chen A, Wu W (2013)

Construction of a novel magnetic targeting anti-tumor drug

delivery system: cytosine arabinoside-loaded bacterial

magnetosome. Materials 6:3755–3763

Dutz S, Hergt R (2013) Magnetic nanoparticle heating and heat

transfer on a microscale: basic principles, realities and

physical limitations of hyperthermia for tumour therapy.

Int J Hyperthermia 29:790–800

Felfoul O, Mohammadi M, Martel S (2007) Magnetic resonance

imaging of Fe3O4 nanoparticles embedded in living mag-

netotactic bacteria for potential use as carriers for in vivo

applications. Conf Proc IEEE Eng Med Biol Soc

1463–1466

Felfoul O, Mokrani N, Mohammadi M, Martel S (2010) Effect

of the chain of magnetosomes embedded in magnetotactic

bacteria and their motility on magnetic resonance imaging.

Conf Proc IEEE Eng Mol Biol Soc 4367–4370

Felfoul O, Mohammadi M, Gaboury L, Martel S (2011) Tumor

targeting by computer controlled guidance of magneto-

tactic bacteria acting like autonomous microrobots. Conf

Proc IEEE Intell Robot Syst 1304–1308

Biotechnol Lett

123

Gambhir SS, Benoit M, Matin AC, Barak Y, Keren S, Mayer D

(2010). US Patent: US, 0135912 A1. Magnetotactic bac-

teria MRI positive contrast enhancement agent and meth-

ods of use

Goldhawk DE, Rohani R, Sengupta A, Gelman N, Prato FS

(2012) Using the magnetosome to model effective gene-

based contrast for magnetic resonance imaging. Wiley

Interdiscip Rev Nanomed Nanobiotechnol 4:378–388

Gorby YA, Beveridge TJ, Blakemore RP (1988) Characteriza-

tion of the bacterial magnetosome membrane. J Bacteriol

170:834–841

Grunberg K, Muller EC, Otto A, Reszka R, Linder D, Kube M,

Reinhardt R, Schuler D (2004) Biochemical and proteomic

analysis of the magnetosome membrane in Magnetospir-

illum gryphiswaldense. Appl Env Microbiol 70:1040–1050

Hafeli UO, Pauer GJ (1999) In vitro and in vivo toxicity of

magnetic microspheres. J Magn Magn Mater 194:76–82

Herborn CU, Papanikolaou N, Reszka R, Grunberg K, Schuler

D, Debatin JF (2003) Magnetosomes as biological model

for iron binding: relaxivity determination with MRI. Rofo

175:830–834

Hergt R, Dutz S, Muller R, Zeisberger M (2006) Magnetic par-

ticle hyperthermia: nanoparticle magnetism and materials

development for cancer therapy. J Phys 18:S2919–S2934

Hoell A, Wiedenmann A, Heyen U, Schuler D (2004) Nano-

structure and field-induced arrangement of magnetosomes

studied by SANSPOL. Phys B 350:E309–E313

Hofer U (2013) A close-up of magnetotactic bacteria. Nat Rev

Microbiol 11:360

Hopkin M (2004) Magnet-making bacteria could target

tumours. Nature. doi:10.1038/news040906-11

Jain RK (2001) New approaches for the treatment of cancer.

Adv Drug Deliv Rev 46:149–168

Jevprasesphant R, Penny J, Jalal R, Attwood D, McKeown NB,

D’Emanuele A (2003) The influence of surface modifica-

tion on the cytotoxicity of PAMAM dendrimers. Int J

Pharm 252:263–266

Katritch V, Abagyan R (2011) GPCR against binding revealed

by modelling and crystallography. Trends Pharmacol Sci

32:637–643

Khalil ISM, Pichek MP, Zondervan L, Abelmann L, Misra S

(2013a) Characterization and control of biological micr-

orobots. In: Desai JP, Dudek G, Khatib O, Kumar V (eds)

Experimental robotics. Springer tracts in advanced robot-

ics, 88th edn. Springer, Zurich, pp 617–631

Khalil ISM, Magdanz V, Sanchez S, Schmidt OG, Abelmann L,

Misra S (2013b) Magnetic control of potential microro-

botic drug delivery systems: nanoparticles, magnetotactic

bacteria and self-propelled microjets. Conf Proc IEEE Ann

Int Conf EMBS 2013:5299–5302

Kingsley JD, Dou H, Morehead J, Rabinow B, Gendelman HE,

Destache CJ (2006) Nanotechnology: a focus on nano-

particles as a drug delivery system. J Neuroimmune Phar-

macol 1:340–350

Kumar AVS, Kumar PG, Shankar S (2009) Role of nuclear

medicine in evaluation and management of joint diseases.

Ind J Rheumatol 4:61–68

Lisy MR, Hartung A, Lang C, Schuler D, Richter W, Reichen-

bach JR, Kaiser WA, Hilger I (2007) Fluorescent bacterial

magnetic nanoparticles as bimodal contrast agents. Invest

Radiol 42:235–241

Liu RT, Liu J, Tong JQ, Tang T, Kong WC, Wang XW, Li Y,

Tan JT (2012) Heating effect and biocompatibility of

bacterial magnetosomes as potential materials used in

magnetic fluid hyperthermia. Prog Nat Sci Mater Int

22:31–39

Liu Y, Xie M, Wang S, Zheng Q, Chen A, Deng Q (2013) Facile

fabrication of high performances MTX nanocomposites

with natural biomembrane bacterial nanoparticles using

GP. Mater Lett 100:248–251

Lu Z, Martel S (2006) Preliminary investigation of bio-carriers

using magnetotactic bacteria. Conf Proc IEEE Eng Med

Biol Soc 1:3415–3418

Luk KH, Drennan T, Anderson K (1986) Potential role of

physical therapists in hyperthermia in cancer therapy: the

need for further training. Phys Ther 66:340–343

Malloy TF (2011) Nanotechnology regulation: a study in claims

making. ACS Nano 5:5–12

Martel S (2006) Towards MRI-controlled ferromagnetic and

MC-1 magnetotactic bacterial carriers for targeted thera-

pies in arteriolocapillar networks stimulated by tumoral

angiogenesis. Conf Proc IEEE Eng Med Biol Soc 1:

3399–3402

Martel S (2010) Microrobotic navigable entities for magnetic

resonance targeting. Conf Proc IEEE Eng Med Biol Soc

5:1942–1945

Martel S (2012) Magnetotactic bacteria for microrobotics. In:

Kim M, Steager E, Agung J (eds) Microbiorobotics: bio-

logically inspired microscale robotic systems. Elsevier,

Oxford, pp 201–210

Martel S (2014) Towards fully autonomous bacterial microro-

bots. Experimental robotics. Springer tracts in advanced

robotics, vol 79. Springer, New York, pp 775–784

Martel S, Felfoul O, Mathieu JB, Chanu A, Tamaz S, Moham-

madi M, Mankiewicz M, Tabatabaei N (2009) MRI-based

medical nanorobotic platform for the control of magnetic

nanoparticles and flagellated bacteria for target interven-

tions in human capillaries. Int J Rob Res 28:1169–1182

Maruyama K (2007) Detection of epidermal growth factor

receptor (EGFR) mutations in non-small cell lung cancer

(NSCLC) using a fully automated system with a nano-scale

engineered biomagnetite. Biosens Bioelectron 22:

2282–2288

Maruyama K, Takeyama H, Nemoto E, Tanaka T, Yoda K,

Matsunaga T (2004) Single nucleotide polymorphism

detection in aldehyde dehydrogenase 2 (ALDH2) gene

using bacterial magnetic particles based on dissociation

curve analysis. Biotechnol Bioeng 87:687–694

Matsunaga T, Higashi Y, Tsujimura N (1997) Drug delivery by

magnetoliposomes containing bacterial magnetic particles.

Cell Eng 2:7–11

Matsunaga T, Takeyama H, Tanaka T, Yoshino T (2004) Jap-

anese Patent: JP 2004290039A. Jpn Kokai Tokkyo Koho.

Manufacture of G protein-coupled receptor (GPCR) with

magnetic bacteria

Matsunaga T, Maruyama K, Takeyama H, Katoh T (2007) High-

throughput SNP detection using nano-scale engineered

biomagnetite. Biosens Bioelectron 22:2315–2321

Mokrani N, Felfoul O, Afkhami ZF, Mohammadi M, Aloyz R,

Batist G, Martel S (2010) Magnetotactic bacteria penetra-

tion into multicellular tumor spheroids for targeted therapy.

Conf Proc. IEEE Eng Med Biol Soc 2010:4371–4374

Biotechnol Lett

123

Munoz-Jimenez A, Clares B, Ruiz MA, Arias JL (2010) Cancer

therapy and diagnosis by magnetosomes. Ars Pharm

51:203–207

Nakamura N, Hashimoto K, Matsunaga T (1991) Immunoassay

method for the determination of immunoglobulin G using

bacterial magnetic particles. Anal Chem 63:268–272

Ota H, Takeyama H, Nakayama H, Katoh T, Matsunaga T

(2003) SNP detection in transforming growth factor-b1

gene using bacterial magnetic particles. Biosens Bioelec-

tron 18:683–687

Patyar S, Joshi R, Byrav DSB, Prakash A, Medhi B, Das BK

(2010) Bacteria in cancer therapy: a novel experimental

strategy. J Biomed Sci 17:21

Sahoo SK, Labhasetwar V (2003) Nanotech approaches to drug

delivery and imaging. Drug Discov Today 8:1112–1120

Schuler D, Frankel RB (1999) Bacterial magnetosomes:

microbiology, biomineralization and biotechnological

applications. Appl Env Microbiol 52:464–473

Schwarz S, Fernandes F, Sanroman L, Hodenius M, Lang C,

Himmelreich U, Schmitz-Rode T, Schuler D, Hoehn M,

Zenke M, Hieronymus T (2009) Synthetic and biogenic

magnetite nanoparticles for tracking of stem cells and

dendritic cells. J Magn Magn Mater 321:1533–1538

Sinha R, Kim GJ, Niel S, Shin DM (2006) Nanotechnology in

cancer therapeutics: bioconjugated nanoparticles for drug

delivery. Mol Cancer Ther 5:1909–1917

Sun JB (2007) In vitro and in vivo antitumor effects of doxo-

rubicin loaded with bacterial magnetosomes (DBMs) on

H22 cells: the magnetic bio-nanoparticles as drug carriers.

Cancer Lett 258:109–117

Sun JB (2009) Targeted distribution of bacterial magnetosomes

isolated from Magnetospirillum gryphiswaldense MSR-1

in healthy Sprague-Dawley rats. J Nanosci Nanotechnol

9:1881–1885

Sun JB, Duan JH, Dai SL, Ren J, Guo L, Jiang W, Li Y (2008)

Preparation and anti-tumor efficiency evaluation of doxo-

rubicin-loaded bacterial magnetosomes: magnetic nano-

particles as drug carriers isolated from Magnetospirillum

gryphiswaldense. Biotechnol Bioeng 101:1313–1320

Sun J, Tang T, Duan J, Xu PX, Wang Z, Zhang Y, Wu L, Li Y

(2010) Biocompatibility of bacterial magnetosomes: acute

toxicity, immunotoxicity and cytotoxicity. Nanotoxicol

4:271–283

Sun J, Li Y, Liang XJ, Wang CW (2011) Bacterial magneto-

some: a novel biogenetic magnetic targeted drug carrier

with potential multi functions. J Nanomater 469031–

469043

Suri SS, Fenniri H, Singh B (2007) Nanotechnology-based drug

delivery systems. J Occup Med Toxicol 2:16

Taherkhani S, Mohammadi M, Daoud J, Martel S, Tabrizian M

(2014) Covalent binding of nanoliposomes to the surface of

magnetotactic bacteria for the synthesis of self-propelled

therapeutic agents. ACS Nano 8:5049–5060

Tang YS (2012) Bacterial magnetic particles as a novel and

efficient gene vaccine delivery system. Gene Ther

19:1187–1195

Tomita-Mitchell A, Muniappan BP, Herrero-Jimenez P, Zarbl

H, Thilly WG (1998) Single nucleotide polymorphism

spectra in newborns and centenarians: identification of

genes coding for rise of mortal disease. Gene 223:381–391

Vereda F, Vicente DJ, Hidalgo-Alvarez R (2009) Physical

properties of elongated magnetic particles: magnetization

and friction coefficient anisotropies. Chem Phys Chem

10:1165–1179

Wagner V, Dullaart A, Bock AK, Zweck A (2006) The

emerging nanomedicine landscape. Nat Biotechnol 24:

1211–1217

Xiang L, Wei J, Jianbo S, Guili W, Feng G, Ying L (2007)

Purified and sterilized magnetosomes from Magnetospir-

illum gryphiswaldense MSR-1 were not toxic to mouse

fibroblasts in vitro. Lett Appl Microbiol 45:75–81

Yan L (2012) Biocompatibility evaluation of magnetosomes

formed by Acidithiobacillus ferrooxidans. Mater Sci Eng,

C 32:1802–1807

Yoshino T, Haruko T, Matsunaga T (2002) Bacterial magnetic

particle surface display of G protein-coupled receptors.

Nippon Kagakkai Baiotekunoroji Bukai Shinpojiumu

Koen Yoshishu 6:40 (in Japanese)

Yoshino T, Takahashi M, Takeyama H, Okamura Y, Kato F,

Matsunaga T (2004) Assembly of G protein-coupled

receptors onto nanosized bacterial magnetic particles using

Mms16 as an anchor molecule. Appl Environ Microbiol

70:2880–2885

Yoshino T, Maeda Y, Matsunaga T (2010) Bioengineering of

bacterial magnetic particles and their applications in bio-

technology. Recent Pat Biotechnol 4:214–225

Biotechnol Lett

123