ALPHANDÉRY ET AL . VOL. 5 ’ NO. 8 ’ 6279–6296 ’ 2011 www.acsnano.org 6279 July 06, 2011 C 2011 American Chemical Society Chains of Magnetosomes Extracted from AMB-1 Magnetotactic Bacteria for Application in Alternative Magnetic Field Cancer Therapy Edouard Alphand ery, †,‡, * St ephanie Faure, ‡ Olivier Seksek, § Franc-ois Guyot, †,^ and Ime` ne Chebbi ‡ † Institut de Mineralogie et de Physique des Milieux Condenses, Universite Pierre et Marie Curie, 4 Place Jussieu, 75005, Paris, France, ‡ Nanobacterie SARL, 36 Boulevard Flandrin, 75016, Paris, France, § Laboratoire ANbioPhy-Fre 3207, Universite Pierre et Marie Curie, 4 Place Jussieu, 75005, Paris, France, and ^ Institut de Physique du Globe de Paris, Universite Paris Diderot, Sorbonne Paris Cite, 1 Rue Jussieu, 75005, Paris, France O ur concept should favor the emer- gence of a new generation of ther- apeutical substance which may be considered as a drug or a medical device depending on medical regulation, the way in which it is used and its behavior in the organism. It relies on the idea that the move- ment, the activation, and the detection of such substance could be controlled exter- nally by a medical device. This approach is of special interest in the field of cancer research since an efficient treatment with limited side effects would require the use of a substance that could be sent specifically within the cancer cells, that could be mon- itored in the organism, for example to verify that the substance is located within the tumor before the treatment is started, and that could be activated on demand by a medical device. A good candidate for such a substance would be magnetic iron oxide nanoparticles. These nanoparticles may in- deed potentially be guided within the cancer cells using a magnetic field, detected using magnetic resonance imaging (MRI) and heated by being exposed to an alternative magnetic field (AMF). 1 In this case, the destruction or elimination of tumors would occur by increasing the tumor tempera- ture typically within the range 37 45 °C for hyperthermia 2 or above 45 °C for thermoablation. 3 In previous work, heating has been induced using chemically syn- thesized nanoparticles, mainly in the form of superparamagnetic iron oxide nanopar- ticles (SPION), which were either mixed in solution or mixed with cells or administered to a living organism. 1 16 The efficiency of this type of thermotherapy has been dem- onstrated on several types of cancers in- cluding brain cancer, 8,9 prostate cancer, 10 13 and breast cancer. 14 16 Research in this area has also led to industrial developments. In addition to the company Nanobacterie, which led to this study, there are at least three companies that develop cancer therapy using the heat generated by magnetic nanoparti- cles when the latter are exposed to an AMF. 17 The patents that have been published by these * Address correspondence to edouardalphandery@hotmail.com. Received for review April 7, 2011 and accepted July 6, 2011. Published online 10.1021/nn201290k ABSTRACT Chains of magnetosomes extracted from AMB-1 magnetotactic bacteria are shown to be highly efficient for cancer therapy when they are exposed to an alternative magnetic field. When a suspension containing MDA-MB-231 breast cancer cells was incubated in the presence of various amounts of extracted chains of magnetosomes, the viability of these cells remained high in the absence of an alternative magnetic field. By contrast, when this suspension was exposed to an alternative magnetic field of frequency 183 kHz and field strengths of 20, 40, or 60 mT, up to 100% of these cells were destroyed. The antitumoral activity of the extracted chains of magnetosomes is demonstrated further by showing that they can be used to fully eradicate a tumor xenografted under the skin of a mouse. For that, a suspension containing ∼1 mg of extracted chains of magnetosomes was administered within the tumor and the mouse was exposed to three heat cycles of 20 min, during which the tumor temperature was raised to ∼43 °C. We also demonstrate the higher efficiency of the extracted chains of magnetosomes compared with various other materials, i.e., whole inactive magnetotactic bacteria, individual magnetosomes not organized in chains, and two different types of chemically synthesized superparamagnetic iron oxide nanoparticles currently tested for alternative magnetic field cancer therapy. The higher efficiency of the extracted chains of magnetosomes compared with that of the other nanoparticles is attributed to three factors: (i) a specific absorption rate higher for the magnetosomes than for the chemically synthesized superparamagnetic iron oxide nanoparticles, (ii) a more uniform heating for the chains of magnetosomes than for the individual magnetosomes and (iii) the ability of the chains of magnetosomes to penetrate within the cancer cells or bind at the cell membrane following the application of the alternative magnetic field, which enables efficient cell destruction. Biodistribution studies revealed that extracted chains of magnetosomes administered directly within xenografted breast tumors progressively left the tumors during the 14 days following their administration and were then eliminated in large proportion in the feces. KEYWORDS: nanotechnology . chains of magnetosomes . magnetic hyperthermia . alternative magnetic field . cancer . thermotherapy . magnetotactic bacteria . biodistribution of ferromagnetic nanoparticles . magnetosome . tumor ARTICLE