Jahresbericht 2005 - IPHT Jena

MAGNETIK & QUANTENELEKTRONIK / MAGNETICS & QUANTUM ELECTRONICS
Fig. 1.18: Magnetic properties in dependence on
number of cycles (i.e. on increasing mean size
from 11 to 26 nm).
realised. Bigger particles in size distributions with
mean values > ≈25 nm are magnetically too hard
to give a high loss power at the small field amplitudes
required for medical treatment.
Experiments on covering the particles by a biocompatible
layer (dextran) were started in the
frame of a diploma thesis. Stable suspensions with
17 nm-particles (mean value) could be prepared.
Investigations on magnetic properties were done
as well in cooperation with partners on Co-particles,
encapsulated particles (FZK, DFG-program),
hard-magnetic Ba-ferrite particles (TU
Ilmenau), iron oxide particles and ferrofluids with
different polymer surface layers (University Düsseldorf,
DFG-program) and iron oxide microspheres
(HKI Jena).
1.2.12 Biomedical applications of magnetic
nanoparticles
(Rudolf Hergt, Matthias Zeisberger)
In the last years magnetic nanoparticles (MNP)
found increasing interest in various biomedical
applications as for instance superparamagnetic
contrast agents for MRI, cellular separation and
refinement, drug delivery, gene magnetofection
and magnetic biochips. One important new therapy
method entering now clinical application is
magnetic particle hyperthermia and thermoablation
which is under development in the group of
the IPHT in co-operation with the Institute for
Diagnostic and Interventional Radiology (IDIR,
Prof. W. A. Kaiser) of the Clinics of the University
Jena. Within the frame of the DFG-priority program
“Colloidal Magnetic Fluids” foundations for
therapy of breast carcinoma by magnetic particle
injection were provided and the fundamentals of
the second therapy generation, the “Antibody
Mediated Targeting of Nanoparticles” (AMTN)
were laid down. The experimental setup developed
in co-operation with IDIR for first clinical trials
was further improved considering reliability
and comfortability for patients. For the developed
apparatus as well the special magnetic particle
suspension to be injected for tumour therapy two
patents were filed.
The new method of AMTN is presently under
investigation in the frame of the DFG-project
“Magnetic heat treatment of breast tumours with
multivalent magnetic nanoparticles” (HE2878/9-2)
in co-operation with Prof. Kaiser (IDIR). The goal
is the coupling of three strategies of tumour therapy:
combination of hyperthermia by magnetic
nanoparticles with antibody-targeting and chemoor
radiotherapy. Therefore, functional molecular
groups (e.g. tumour-specific antibodies and cisplatin)
will be coupled to the carboxymethyldextran
coating of maghemite nanoparticles. There, a till
now not satisfyingly solved problem is the preparation
of MNP which provide sufficient specific
heating power (SHP). While suitable MNP with
moderate values of SHP are available now for the
direct intratumoural injection method, the target
concentrations expected for AMNT are so low that
at least an order of magnitude higher SHP is
needed. Theoretical modelling of the heat generation
by magnetic nanoparticles in a tumour
showed that for large tumours (some cm) SHP of
more than 1 kW/g is needed, a value which is even
increasing with decreasing tumour size. Such a
high value of SHP was found by our group till now
only for magnetosomes synthesized by magnetotactical
bacteria (co-operation with Dr. Schüler,
MPI Marine Microbiology Bremen). Unfortunately,
those particles are available only in small amounts
and – more importantly – they lack biocompatibility
due to the bacteria proteins of their coating. Our
investigations have shown that a maximum of
magnetic losses occurs in the transition region
between superparamagnetic and stable single
domain particles. For maghemite or magnetite this
is just the mean size of about 30 nm found for
magnetosomes. However, screening with respect
to magnetic properties, in particular losses, for
various MNP types prepared by chemical precipitation
resulted in nearly one order of magnitude
lower SHP. As a reason, the too broad size distribution
as well as a magnetic coupling of MNP is
supposed and is subject of present investigations.
Besides efforts with particle preparation described
in the previous section. An apparatus for magnetic
size fractionation was developed which is under
investigation, now. Another way towards large values
of SHP is the application of MNP with higher
magnetic moment e.g. FePt or Co. The latter ones
are presently magnetically investigated with
encouraging results (co-operation with Prof. Bönnemann,
FKZ).
In co-operation with the University of Applied Sciences
Jena (Prof. Andrä, Prof. Bellemann, Dept.
Biomedical Engineering) a pharmaceutical capsule
for the remote controlled drug release is in
development. The release mechanism is based
on the heating of a magnetic absorber in an alternating
magnetic field. By in-vitro investigations
the remote controlled release was realised and a
clinical study is under preparation.
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