ABSTRACTS – ORAL PRESENTATIONS - AMCA, spol. s r.o.

P51. FLUORESCENCE-LABELED FERROMAGNETIC NANOPARTICLES FOR MRI-GUIDED
MAGNETIC FLUID HYPERTHERMIA-BASED GLIOBLASTOMA TREATMENT AND MR
IMAGING
Karolina Turnovcova 1 , Vit Herynek 2 , Emil Pollert 3 , Pavel Veverka 3 , Pavel Zvatora 4 , Magda
Vosmanska 4 , Daniel Jirak 2 , Milan Hajek 2 , Eva Sykova 1 , Pavla Jendelova 1
1
Institute of Experimental Medicine ASCR, Prague, Czech Republic, karolina.
turnovcova@biomed.cas.cz
2
MR-Unit, Department of Radiodiagnostic and Interventional Radiology, Institute for
Clinical and Experimental Medicine, Prague, Czech Republic
3
Institute of Physics, ASCR, Prague, Czech Republic
4
The Institute of Chemical Technology, Prague, Czech Republic
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor
occuring in humans, and its cells are resistant to conventional therapy. Fluorescencelabeled
ferromagnetic nanoparticles may serve for both diagnostic and therapeutic
purposes. They represent intracellular labeling using endocytosis uptake, are a suitable
contrast agent for magnetic resonance imaging (MRI) in vivo, and can also be used for
guided temperature-controlled thermoablation. The method is based on the deposition
of stable and nontoxic suspensions of the magnetic nanoparticles inside the tumor
followed by exposure to a high frequency (HF) electromagnetic field. Magnetic hysteresis
losses result in local heating by the particles and consequently to the apoptosis of the
cells.
Perovskite nanoparticles (La 1-x
Sr x
MnO 3
), coated by SiO 2
with FITC, were synthesized, their
surface was modificated with different materials [chitosan, 2-[methoxy(polyethyleneoxy)
propyl]trimethoxysilane (PEET)], and they were tested in vitro and in vivo.
Rat and human mesenchymal stromal cells (rMSC, hMSC) and GBM cell lines (C6, A172
and GaMG) were cultivated with nanoparticles for 48 hours using the xCELLigence System;
the real-time growth curves were recorded, and the culture viability was analysed by
trypan blue staining. The nanoparticle uptake into the cells was then analysed using
FACS-based fluorescence intensity measurements and directly by ICP-MS spectrometry.
The viability of cells incubated with the nanoparticles was in the range of 60 – 95%,
whereas a control sample reached 98%. The amount of incorporated nanoparticles was
up to 10-fold higher in the GBM cell lines and was affected by surface modification.
Two million C6 cells were injected intradermally into rats (n=10). In 2 weeks, 50 ul of a
4 mM Mn suspension of perovskite nanoparticles was injected into the glioblastoma
tissue. MRI images were obtained to confirm the distribution of the nanoparticles in
the tumor. The rats were exposed to a HF electromagnetic field (480 kHz, 11 mT) for
30 minutes. Four control animals with tumors underwent HF field exposure without
nanoparticles, or the application of nanoparticles without exposure to the HF field. The
temperature in the tumor with nanoparticles increased to 41.7°C, while control animals
without nanoparticles reached 40°C. Immunohistochemistry (staining for caspase3
and TUNEL) revealed massive apoptosis in the tumors of the animals with injected
nanoparticles after exposure to the HF field.
148 Analytical Cytometry VII