June 8, 2016

The Japan Society of Mechanical Engineers
Hokkaido Branch“Biomechanics Research Meeting”
23rd Seminar
Chairman: Toshiro Ohashi

The Biomechanics Research Meeting will sponsor a presentation by Prof. M. Ricardo Ibarrafrom University of Zaragoza, Spain. Faculty members, graduate students, and undergraduates
are encouraged to participate in the seminar.
Date&Time: June 24, 2016, 11:00-12:00
Place: Room#A1-17, Faculty of Engineering, Hokkaido University
http://www.eng.hokudai.ac.jp/building/?place=outer
Speaker: Prof. M. Ricardo Ibarra, Ph.D.
University of Zaragoza, Spain
Title: Magnetic nanoparticles for new therapies and diagnosis
Magnetic nanoparticles (MNPs) constitute nowadays a vast field of research due to thecurrent and expected application in nanobiomedicine. The potential MNPs stems from theintrinsic properties of their magnetic cores, combined with the functionality acquired under anappropriate coating. The capability for loading and targeted controlled release of drugs is oneof the main issues in cancer therapy (for recent reviews see [1,2]). The biofunctionalization ofthe nanoparticles surface make them suitable for magnetic separation based on thebiomolecular recognition of biological moieties. New inmunomagnetic assays using magnetic
nanoparticles provides a new route to quantize the results in biosensors. The presence ofMNPs also perturb locally the hydrogen proton relaxation, this phenomenon is on the bases ofthe enhance MRI diagnostic using contrast agents. Targeting of these contrast agents could
detect angiogenesis processes at early stages.
In this talk a brief review of all these different applications will be depicted emphasizing
the application of electromagnetic waves in new therapies based on magnetic hyperthermia.
The case of dendritic cells (DCs) as main candidate for magnetic hyperthermia will bereported. Magnetic hyperthermia (MH) is based on the use of MNPs to selectively increase
the temperature of MNP-loaded target tissues when applying an alternating magnetic field(AMF) in the range of radiofrequency. To date, all MH research has focused on heatgeneration in an attempt to elucidate the mechanisms for the death of MNP-loaded cells
submitted to AMF. However, recent in vitro studies have demonstrated the feasibility ofinducing dramatic cell death without increasing the macroscopic temperature during AMF
exposure. Here, we show that the cell death observed following AMF exposure, specificallythat of MNPs loaded dendritic cells (DCs) in culture, was caused by the release of toxic

agents into the cell culture supernatants and not due to a macroscopic temperature increase[3].
We performed MH in vitro experiments to demonstrate that the supernatant of the cell culture
following AMF exposure was highly toxic when added to control unloaded DCs, as thistreatment led to nearly 100% cell death. Therefore, our results demonstrate that heat is not theonly agent responsible for triggering cell death following MH treatment. This finding offers
new perspectives for the use of DCs as the proverbial Trojan horse to vectorise MNPs to thetarget tumour area and these results further support the use of DCs as therapeutic agentsagainst cancer when submitted to AMF. Furthermore, this discovery may help inunderstanding the mechanism of cell death mediated by exposure to AMF.
[1] “Magnetic nanoparticles for drug delivery” M. Arruebo, R. Fernandez-Pacheco, M.R.
Ibarra and J. Santamaría. Nanotoday 2 (2007) 22[2] “Magnetic nanoparticles for cancer therapy” G.F: Goya, V. Grazu and M.R. Ibarra.
Current Nanoscience 4 (2008) 1-16
[3] “Induced cell toxicity originates dendritic cell death following magnetic hyperthermiatreatment” L Asín, G F Goya, A Tres & M R Ibarra. Cell Death and Disease 4,e596 doi:10.1038/cddis.2013.121 (http://www.nature.com/cddis)

Contact:Toshiro Ohashi
Division of Human Mechanical Systems and Design, Faculty of Engineering, HokkaidoUniversity
Tel&Fax: 011-706-6424, Email: ohashi@eng.hokudai.ac.jp