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Contrast Media Mol Imaging. 2016 Nov;11(6):514-526. doi: 10.1002/cmmi.1713. Epub 2016 Sep 22.

Improved specific loss power on cancer cells by hyperthermia and MRI contrast of hydrophilic Fex Co1-x Fe2 O4 nanoensembles.

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Magnetic Resonance Research Center (MRRC) and Quantitative Neuroscience with Magnetic Resonance (QNMR) Core Center, Yale University, New Haven, CT, USA.
Department of Radiology & Biomedical Imaging, Yale University, New Haven, CT, USA.
Materials Science Division, Bangladesh Atomic Energy, Dhaka, Bangladesh.
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University, New Haven, CT, USA.
Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
Department of Radiology, Michigan State University, East Lansing, MI, USA.


Ferrite-based ferri/superparamagnetic nanoparticles can be rapidly heated by an external alternating magnetic field (AMF) to induce tissue necrosis of the adjacent microenvironment, but in addition provide magnetic resonance imaging (MRI) contrast utilizing enhanced water relaxivity. Here we characterized nanoensembles of Fe-Co mixed spinel ferrites (i.e. Fex Co1-x Fe2 O4 , where x ranges from 0.2 to 0.8) synthesized by chemical co-precipitation. With nanoensembles of increasing Co content the saturation magnetization improved, while lattice parameter remained relatively constant. MRI water (transverse) relaxivity at 11.7 T was also boosted with increasing Co content. Efficiency of AMF-induced heating was quite comparable for the nanoensembles with either chitosan or polyethylene glycol (PEG) coating except for PEG-coated Fe0.2 Co0.8 Fe2 O4 , which was twice as less efficient as others. While toxicity of the nanoensembles with either coating examined on 9L tumor cell cultures showed no significant differences, upon AMF exposure (i.e. heat-induced necrosis) Fex Co1-x Fe2 O4 composition with different values of x showed quite dramatic effects on cell death of tumor cells with both coatings. This study lays the ground work for further characterization of other mixed spinel ferrites, and in addition we expect that chitosan and PEG coated Fex Co1-x Fe2 O4 of all the compositions will have good potential for preclinical applications in vivo.


9L gliosarcoma cells; MRI contrast agent; PEG; chitosan; hydrophilic; nanoensembles; nuclear magnetic resonance; specific loss power

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