Volume 8 - 2021 | <a class="ArticleLayoutHeader__info__doi" href="https://doi.org/10.3389/fmats.2021.638019">https://doi.org/10.3389/fmats.2021.638019</a>
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we explored the magnetic hyperthermia performance of condensed&#x02013;clustered magnetic iron oxide nanoparticles (MIONs) in the range of 400  kHz to 1.1 MHz at low field amplitudes
can influence the hyperthermia power produced by MIONs
with a fixed magnetic field strength of 3 mT is recorded
revealing a direct relationship between the two physical quantities and a high heating efficiency for the condensed&#x02013;clustered MIONs
the specific loss power (SLP) (or specific absorption rate [SAR]) parameter
which is the ratio of the heat power in watts produced per nanoparticle mass in grams
is linear to a good degree to the oscillating frequency with a step of roughly 30 W/g per 100 kHz increase
all the measurements were within the safety limits proposed by Hergt and Dutz criterion of H f &#x02264; 5 &#x000D7; 109 A/ms for clinical application of magnetic fluid hyperthermia (MFH)
time at each frequency were interpreted in terms of simple thermodynamic arguments
thus extracting useful thermodynamic parameters for the heat power generated by the condensed&#x02013;clustered MIONs
the widely different experimental conditions (i.e.
have led to the introduction of another parameter called &#x0201C;intrinsic loss power&#x0201D; (ILP) which is defined as
the experimental evaluation of hyperthermia agents remains the most valid route for the extraction of SLP and related hyperthermia parameters
especially for strongly interacting systems with a high interest for the applications of magnetic hyperthermia
such as the condensed&#x02013;clustered MIONs
no such resonance was observed in our case and the measured temperature was proportional to the applied frequency
This could be explained by the increased interparticle interactions of the condensed magnetic clusters
Typical parameters used in hyperthermia experiments
Iron(II) sulfate heptahydrate (Fe2SO4 &#x000D7; 7H2O
viscosity of 2% solution at 25&#x000B0;C: &#x0007E;250 cps)
and ultrapure water (conductivity of &#x0007E;1 &#x003BC;S/cm) prepared with an SG ultrapure water system were used for the synthesis of the MNPs
For the synthesis of the MIONs, we followed the protocol presented in our earlier study (<a href="#B50">Zoppellaro et al., 2014</a>)
which is quoted here for the convenience of the reader: Briefly
alkaline precipitation of MIONs was performed from a single ferrous precursor of Fe2SO4 &#x000D7; 7H2O in the presence of sodium alginate at 50&#x000B0;C
300 mg of alginate was dissolved in deionized H2O (60 mL)
30%) was added to the solution followed by 1,440 mg of FeSO4 &#x000D7; 7H2O (in 20 mL of H2O containing 60 &#x003BC;L of 37% HCl)
The mixture was heated at 50&#x000B0;C under magnetic stirring for 80 min
The final product (denoted as MagAlg) was purified and fractionated by centrifugation
The resulting solution used for the measurements had a concentration of 2.5 mg/mL in Fe2O3
The morphology of the synthesized nanoparticles was investigated by transmission electron microscopy (TEM)
wherein samples were prepared by casting a droplet of a dilute aqueous suspension of nanoparticles (0.01% w/v in Fe2O3) on copper grids coated by a Formvar carbon film
The determination of the hydrodynamic diameter (Dh) of nanoparticles dispersed in deionized H2O was performed with a ZetaSizer Nano series Nano-ZS (Malvern Instruments Ltd.
UK) equipped with a He&#x02013;Ne laser beam at a wavelength of 633 nm and a fixed backscattering angle of 173&#x000B0;
The concentration of the measured colloids was 0.0125% w/v (g/100 mL) in Fe2O3
The zeta potential of the nanoparticles was assessed with the same instrument as the average of 100 runs with the phase analysis light scattering (PALS) mode
<a href="#F1">Figure 1</a> shows our setup used for hyperthermia experiments which are composed of the following devices:
A custom-designed High Frequency Resonator Unit (KEL
Matching ceramic capacitors of high voltage
one with 20&#x02013;120&#x000B0;F range (H-B Durac Plus Pocket Liquid-in-Glass Thermometer) and another with 20&#x02013;100&#x000B0;C range
MNPs solution inside a glass vial (our sample)
(A) Schematic and (B) photograph showing the whole setup and (C) photograph showing the sample surrounded by the detection coil and two thermometers
The Resonator Unit was connected to the RLC circuit which was formed by the resistance and the inductance of the excitation coil together with the capacitance of the capacitor. The circuit was brought to resonance to get the maximum current to the coil and thus a maximum magnetic field. To achieve a broad range of resonance frequencies, the matching capacitor had the following preset values as summarized in <a href="#T2">Table 2</a>
which when they were combined with the inductance 3.27 &#x000B1; 0.04 &#x003BC;H of the excitation coil
resulted in the resonance frequencies in the range of 400 to 1075 kHz
The excitation coil of length 3.9 cm was composed of 8 turns each with a diameter of 4.2 cm and it was made of copper wire of 1.05 mm diameter integrated with a cooling fin in order to be easily air-cooled by a nearby fan
the voltage of the resonator was adjusted so as to have a constant magnetic field of 3.0 &#x000B1; 0.1 mT
which was measured indirectly by the induced voltage of a single-turn detection coil
since the high frequencies produce enough high voltages to be recorded on the oscilloscope
Two different alcohol thermometers were used for the temperature measurements
one of which was directly immersed in the sample solution to record hyperthermia phenomena and the other to record the air temperature inside the detection coil
in order to ensure that temperature rises in the first coil were emerging from the solution itself and not the coil self-heating
The presence of high-frequency magnetic fields inside the detection coil makes it impossible to use conventional thermometers such as thermocouples or resistance temperature detectors
since they contain metals that will develop induced voltages with corresponding reading errors
the traditional alcohol thermometers were used and their values were read with the help of a magnifier in order to get more precise readings
The aim of this study was to record temperature rises in the MNP solutions at different frequencies and at different exposure times
in order to observe the effect of the exciting field frequency on the hyperthermia phenomenon
which has the form of a solution in a sealed glass vial
was removed from the refrigerator where it was kept at a low temperature of 5&#x000B0;C so as to be chemically inert
&#x02022; The sealed vial was placed in an ultrasonic bath to homogenize and eliminate the agglomerations which were sometimes created during measurements
Magnetic particles tended to accumulate together due to their mutual magnetic attraction to each other
the vial was placed at the center of the excitation coil and one of the thermometers was brought into contact with the solution through a snag hole on the vial lid
&#x02022; The second thermometer was held by a clamp so as to have its measuring tip inside the excitation coil but not in contact with the glass vial
&#x02022; The matching capacitance was set to an appropriate value so as to achieve the desired frequency
&#x02022; Enough time was given to the sample (30 min) with no AC field present
to be brought to a thermal equilibrium with its environment
its initial temperature &#x003B8;0 was recorded
&#x02022; The resonator was then turned on and its output voltage was adjusted so as to have a value of an AC magnetic field equal to 3.0&#x000B1;0.1 mT
This happened when the timer was set to zero
&#x02022; The temperatures &#x003B8; and &#x003B8;air of the two thermometers (sample and air correspondingly) were recorded every minute for a total period of 10 min
&#x02022; The resonator was then turned off at t = 10 min and the vial was shaken by hand
to avoid agglomeration and to have a homogeneous solution without precipitations
&#x02022; The last five steps were repeated with a new frequency
the Ms value remains large (63.06 Am2kg&#x02212;1) without the appearance of a coercive field
these results translate into the possible implementation of the MagAlg system in hyperthermia treatments
that thorough in-vitro and in-vivo studies are required to establish the biocompatibility/safety of the MagAlg nanoparticles for any potential biomedical applications
(a&#x02013;e) HR-TEM micrographs of the MagAlg MNPs
with diffraction rings indexed for inverse spinel iron oxide (maghemite phase)
(f) shows the intensity distributions of the mean hydrodynamic diameter and (g) the zeta potential in water of the MagAlg nanoparticles
(h) shows the saturation magnetization (Ms) vs
applied field (B) for MagAlg recorded at T = 300 K
Concerning the calorimetric measurements of this study, <a href="#F3">Figure 3</a> shows the &#x00394;&#x003B8;10 = &#x003B8;(10) &#x02212; &#x003B8;(0) data
where &#x003B8;(10) is the final and &#x003B8;(0) is the initial temperature for the 10-min interval
for the range of frequencies of 400 to 1075 kHz that our resonator was able to cover
The strength of the magnetic field was kept fixed at 3 mT (2.4 kA/m)
The top data correspond to the MIONs solution temperature and the bottom to the air temperature inside the coil
It is noted from this graph that &#x00394;&#x003B8;10 for MNPs increases roughly linearly with the frequency
while the air temperature is practically constant
the &#x00394;&#x003B8;10 data are fitted better to a second-degree polynomial with an intercept at zero frequency equal to 1.4&#x000B0;C which is within the error range in the graph so it can be assumed as zero
as expected for a zero frequency field (DC field)
it is concluded that the high-frequency AC current does not heat up the coil and subsequently the air inside it (remember that the coil is air-cooled externally by the help of its fins) and that any significant rise in the temperature in the graph is entirely due to the hyperthermia of the MIONs solution
Similar experiments performed in our lab with water replacing the MIONs solution (data not shown) confirm this conclusion as there were no temperature changes recorded by both thermometers
&#x00394;&#x003B8;10 = &#x003B8;(10) &#x02212; &#x003B8;(0) between the final and the initial temperatures for the 10-min interval vs
To examine the time dependence of the hyperthermia effect, we plotted in <a href="#F4">Figure 4</a> the &#x00394;&#x003B8; = &#x003B8;(t) &#x02212; &#x003B8;(0) data vs
time for different frequencies in the range of 400 to 1075 kHz
It is obvious from this graph that &#x00394;&#x003B8; increases with both time and frequency
&#x00394;&#x003B8; seems to achieve saturation during the time interval of 10 min in our experiment
This is typical with heating experiments in which the system always reaches a time-standing condition where the temperature no longer changes with time
It will be shown in the next subsection that the &#x00394;&#x003B8;(t) curve has an exponential dependence from which the important parameters of the solution
such as the heat power and the saturation temperature
time with respect to the initial temperature at t = 0min
and a temperature &#x003B8; which is assumed to be a function of time t
According to Newton&#x00027;s law of cooling
the solution loses heat at a rate of hA(&#x003B8; &#x02212; &#x003B8;0)
A the surface area through which the transfer takes place
and &#x003B8;0 is the surrounding temperature
let a heat source (the hyperthermia) supplying the solution with a heat rate QH&#x02219; (heat per time)
Even though this is an internal heat source
it can be assumed as an external source in order to better understand the thermal physics of the system
let the solution exchange an amount dQ of total heat with its surrounding (cooling plus warming) within a time interval dt
Then its heat rate dQdt will be equal to the sum of the above two rates
one being negative as it describes heat loss and the other being positive as it describes heat gain:
From the definition of the specific heat c
where d&#x003B8; is an incremental change of &#x003B8; upon an incremental exchange of heat dQ
Substituting this expression in Equation 3
it results in a first-order linear differential equation (DE) on &#x003B8;(t):
This DE can be easily solved for &#x00394;&#x003B8;(t) = &#x003B8;(t) &#x02212; &#x003B8;0 as
it will be assumed that there are two different solution masses
the initial mass m1 corresponding to k1 and the final mass m2 corresponding to k2
As our aqueous solution of 2.5 mg/mL is quite dilute
it can be safely assumed that its density is close to the water density of 1.0 g/mL and from it
we can calculate the two masses using the solution volumes as m1 = 4.4 g and m2 = 3.7g
Figure 5. Fitting of Equation 3 in the data of <a style="color:grey;" href="#F3">Figure 3</a>
Table 3. Results of the fit of Equation 3 in the data of <a style="color:grey;" href="#F3">Figure 3</a>
Figure 6. Fitting parameter. of Equation 3n the data of <a style="color:grey;" href="#F3">Figure 3</a> vs
Equations 6 and 7 can be combined to get the hyperthermia heat produced per unit time QH&#x02219; as follows:
Note that from Equation 5 it can be easily seen that the initial slope is equal to k&#x00394;&#x003B8;s
Equation 8 is in agreement with Equation 1 above
The only thing missing to convert QH&#x02219; to SLP is to convert the total solution mass m to the mass fraction &#x003BC; = mn/m
This is easily done by using the water density &#x003C1; = 1.0 g/mL by denoting &#x003BC; = mn/&#x003C1;v = x/&#x003C1; where x is our MNP concentration of 2.5 mg/mL and v is the solution volume
the SLP values were derived at higher magnetic fields (&#x0007E;4 times higher) and with more concentrated samples (an order of magnitude higher)
highlighting the superior performance of condensed&#x02013;clustered MIONs employed for the present study compared with non-clustered systems
we evaluated the hyperthermia efficiency of condensed&#x02013;clustered MIONs in a wide frequency range
there is a direct relationship the power produced by the condensed&#x02013;clustered MIONs on
which is the ratio of the heat power in Watts produced per MNP grams
is linear to a good degree to the frequency with an increase of roughly 30W/g per 100kHz
This linearity can be interpreted in the frame of the inherent strong interparticle interactions in such ensembles
resulting in the coupling of the Brownian and N&#x000E9;el processes
thus shifting the resonance of the condensed&#x02013;clustered MIONs to lower frequencies away from the ones usually employed for in-vivo magnetic hyperthermia
The recorded SLP values were in the 100 to 300 W/g range of which is in agreement with the previous reports
the lower magnetic field employed in the present study highlights the enhanced heating efficiency of condensed&#x02013;clustered MIONs
The produced heat rate Q&#x02219;H was extracted by a simple thermodynamic analysis where the fit parameters are related to different physical quantities
time curves show a simple exponential rise&#x02013;saturation behavior
For the majority of studies reported in the literature
as it is hard to produce high magnetic fields at these frequencies
we were able to use a 3mT field (2.4kA/m) over a frequency scan of 400 kHz to 1.1 MHz being always within the safety limits as proposed by the Hergt and Dutz criterion of H.f &#x02264; 5 &#x000D7; 109A/ms for the clinical application of magnetic hyperthermia
Evaluating the heating performance of condensed&#x02013;clustered MIONs at higher frequencies and low magnetic field amplitudes can provide invaluable information for their potential use as magnetic hyperthermic agents in cases where low magnetic fields or low nanoparticle doses are required for safety reasons
The raw data supporting the conclusions of this article will be made available by the authors
DK: experiment design and theoretical model
GS: experiment design and hyperthermia measurements
AK-N: synthesis of nanoparticles and hyperthermia measurements
GZ: synthesis of nanoparticles and characterization of nanoparticles
All authors contributed to the article and approved the submitted version
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest
GZ acknowledges the support from the ERDF project Development of pre-applied research in nanotechnology and biotechnology (No
AK-N acknowledges the support from Alexander S
Onassis Public Benefit Foundation (Grant No
as well as from the Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Technology (GSRT)
DK would like to thank Stelios Roudis and K.E.L
Company for the custom design and construction of the RF resonator according to our needs
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Zoppellaro G and Spiliotopoulos K (2021) Magnetic Hyperthermia in the 400&#x02013;1,100 kHz Frequency Range Using MIONs of Condensed Colloidal Nanocrystal Clusters
Received: 06 February 2021; Accepted: 09 April 2021; Published: 05 May 2021
Copyright &#x000A9; 2021 Kouzoudis, Samourgkanidis, Kolokithas-Ntoukas, Zoppellaro and Spiliotopoulos. This is an open-access article distributed under the terms of the <a rel="license" href="http://creativecommons.org/licenses/by/4.0/" target="_blank">Creative Commons Attribution License (CC BY)</a>
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&#x0002A;Correspondence: Dimitris Kouzoudis, <a id="encmail">a291em91ZGlAdXBhdHJhcy5ncg==</a>
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Magnetic iron oxide nanoparticles (MIONs) have established a niche as a nanomedicine platform for diagnosis and therapy
but they present a challenging surface for ligand functionalization which limits their applications
coating MIONs with another material such as gold to enhance these attachments introduces other complications
Incomplete coating may expose portions of the iron oxide core
or the coating process may alter their magnetic properties
We describe synthesis and characterization of iron oxide/silica/gold core-shell nanoparticles to elucidate the effects of a silica-gold coating process and its impact on the resulting performance
small angle neutron scattering reveals silica intercalates between iron oxide crystallites that form the dense core
likely preserving the magnetic properties while enabling formation of a continuous gold shell
The synthesized silica-gold-coated MIONs demonstrate magnetic heating properties consistent with the original iron oxide core
with added x-ray contrast for imaging and laser heating
They are thus the subject of considerable research effort to develop multifunctional capabilities
No formulations developed to date have demonstrated combined x-ray and magnetic imaging properties within a single nanoparticle construction that also provides heating with magnetic fields and light
The functionalities of these heterogeneous nanoparticle composites vary greatly due to significant differences in the characteristics of the interfacial structure on the nanoscale
what structural and magnetic changes result from coating the MIONs
to aid optimization of synthesis methods and to validate the resulting product for its intended end-use
Detailed magnetic and structural analysis of the silica- and gold-silica-coated MIONs revealed the MION cores were coated by the silica layer in a manner contrary to current expectations for a dense core
silica intercalated between the individual iron oxide crystallites within the dense solid core instead of encapsulating the entire iron oxide polycrystalline core as a single entity
The silica surface of the elliptical composite facilitated formation of a continuous gold shell
Magnetic characterization and heating with alternating magnetic fields confirmed that the original magnetic properties of the MIONs were only modestly altered
presumably because the silica effectively passivated the MION crystallite surfaces limiting further change in subsequent gold precipitation and reduction reactions
MRI and x-ray CT contrast were characterized for the gold-silica-MIONs and were compared with the precursor constructs
confirming the dual-modality imaging capabilities and extending the range of concentration for MION detection
Heating performance with both magnetic fields and laser was characterized
and proof-of-concept in vivo imaging and heating of a mouse subcutaneous xenograft model of human prostate cancer were demonstrated
A schematic of the chemistry and coated particle structure, and summary of samples prepared and measurements conducted are provided in Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/articles/s41598-018-29711-0#Fig1">1</a>, (AuSi-MION, 3) and in Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/articles/s41598-018-29711-0#Tab1">1</a>, respectively.
</a>Synthesis schematic of gold-silica-coated MIONs
1) were coated with silica using tetraethylorthosilicate to form Si-MIONs (2)
The Si-MIONs were amine-terminated using 3-aminopropyltrimethoxysilane and seeded by a colloidal gold solution containing 1–2 nm gold seeds
a gold shell was grown on the surface by the reduction of chloroauric acid to form AuSi-MIONs (3)
</a>Physical characterization of MIONs. (a) Dynamic light scattering (DLS) of (1) JHU MIONs – 55 nm, (2) Si-MIONs – 81 nm and (3) AuSi-MIONs – 145 nm. (b) SQUID magnetometry measurements of magnetization of MIONs as a function of external field strength. Data are normalized by total solid content, without removal of the silica and gold contributions. (c) Transmission electron microscopy (TEM) of (1) JHU MION cores, (2) silica-coated MIONs and (3) gold and silica-coated MIONs.
</a>Small angle neutron scattering (SANS) data and analysis of MION size and shape
(a) SANS scattering data (points) with correlated model fits (solid lines) obtained using dimensions and 3D geometrical models for JHU MIONs (black squares)
and AuSi-MION (blue triangles) as shown in (b)
Graphics of nanoparticle constructs are used with permission from A.K
and TEM provided no evidence consistent with the formation of pure silica or pure gold nanoparticles
though the local encasement of the iron oxide crystallites with silica was preserved
Use of the shape parameters obtained from SANS fitting enabled reconciliation of differences observed between the DLS and SANS data interpretation
When ellipsoidal objects were considered with interpreting the DLS model
namely that DLS presumes a spherical particle and is most sensitive to the median dimension of an ellipsoid
agreement between DLS and SANS ellipsoid models resulted (see Supplemental information)
Field-dependent magnetization measurements of the JHU MION constructs demonstrated that magnetization saturation (Ms) of AuSi-MIONs was reduced to about 30% of the uncoated JHU MIONs Ms, when normalized to total solid content (Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/articles/s41598-018-29711-0#Fig2">2b</a>)
as the gold and silica provide only a diamagnetic contribution which was not subtracted and the additional mass of the gold and silica are expected to reduce Ms accordingly
An additional contribution to the decreased Ms (see Supplemental Materials) originates from background contributions that cannot be properly accounted because of silica intercalation
precise comparisons of magnetization among the samples is precluded
however it is possible to extract general features from a comparison
When examining the coercivity at 5 K (see Supplemental Material)
there is an initial increase from 24 kA/m for the JHU-MIONs to 32 kA/m for the Si-MIONs
which can be most readily attributed to the rigid encapsulation of the MIONs in silica
however the coercivity returns to its previous value of 24 kA/m
These results suggest that the Au coating has a modest effect on the magnetic properties of the MIONs
Imaging of gel phantoms over a range of 0–80 μg/ml (0–1.4 mM) based on iron content
showing T2 effect as iron concentration increases (top)
T2 relaxation (ms) calculated from spin-echo MR imaging of phantoms (bottom)
Inset shows concentration (mM) versus 1/T2
the slope of which gives transverse relaxivity (R2) in units of mM−1 s−1
(b) Signal intensity from MION phantoms over a range of 0–7 mg/ml (based on iron content) demonstrating CT contrast with gold (top)
was calculated for each sample and were plotted versus iron concentration (bottom)
Adding x-ray opacity to magnetic iron oxide nanoparticles has significant benefit for imaging-guided therapy (hyperthermia) applications because tissue concentrations required
often produce artifacts with magnetic resonance which is more sensitive to the magnetic moments of magnetic iron oxide nanoparticles making it difficult to reliably image tissue concentrations &gt;0.1 mg Fe/g tissue
A magnetic iron oxide construct having both x-ray opacity and significant responsiveness to an alternating magnetic field provides significant benefit for imaging-guided magnetic hyperthermia
and nanoparticle accumulation in response to static field
(a) Photograph showing AuSi-MIONs drawn by four permanent magnets (dotted outlines) demonstrating potential for magnetic localization
(b) Illustration of potential for magnetic localization
Images of liver cancer and big red magnet are used with permission from Dreamstime.com LLC
</a>SLP in AC magnetic field and SAR in laser
a measure of heating efficiency in an alternating magnetic field
Si-MIONs (diamond) and AuSi-MIONs (triangle) at a frequency of 150 kHz ± 5 kHz over a range of amplitudes from 10 to 80 kA/m
reported as specific absorption rates (SARs
normalized by iron content) between JHU MIONs and AuSi-MIONs
A 5.5 W laparoscopic laser was centered on each solution for 15 seconds
The change in temperature was monitored and SARs were calculated for each sample
Comparison of these results confirms that the laser-induced temperature increase is significantly enhanced with gold coating
although the iron oxide core can generate modest heat when exposed to laser energy
This provides additional evidence of the continuity of the gold coating
</a>Histology of prostate tumor xenografts
(a) Mice were euthanized and tumor tissues were collected for staining 72 h post AMF exposure (Row I: H&amp;E
row II: Prussian blue and row III: silver enhancement stain)
The control shows no iron oxide or gold present
Tissues from the mouse injected with JHU MIONs show iron oxide particles in the H&amp;E stain
iron staining (blue) with Prussian blue and no response to the silver enhancement stain
Tissues from the mouse injected with AuSi-MIONs show a dark purple color from the gold nanoparticles in the H&amp;E stain and iron staining (blue) with Prussian blue
Dark black staining of the AuSi-MIONs by the silver enhancement stain
Whole tumor images are composites created from separate 4x images; magnified images were obtained at 20x
we report the synthesis and physical characterization of a magnetic iron oxide nanoparticle construct in which magnetic properties of iron oxide cores are not unduly impacted
and new functionality is added by silica then gold coating to achieve multi-modal imaging and heating capability using a single nanoparticle system
Comprehensive physico-chemical characterization with multiple techniques
confirmed a continuous gold layer and revealed unexpected silica intercalation with the dense polycrystalline MION cores
This silica intercalation promoted formation of a continuous gold coating while preserving the magnetic behavior
The sensitivity of magnetic resonance can be used to detect low concentrations of the Au-Si-MIONs in tissue
while the gold shell enables x-ray visualization of higher nanoparticle concentrations needed for therapeutic applications
Magnetic properties sufficient for remote localization with gradient magnetic fields and heating with alternating magnetic fields were demonstrated
as well as additional heating capability with laser activation
This work demonstrates for the first time a continuous gold-silica coating of magnetic iron oxide nanoparticles in which the magnetic properties are preserved sufficient to retain significant hysteresis heating capability
We also note the critical need for accurate and correct physical and magnetic characterization of nanostructured materials
free of assumptions typically encountered when coating
The identification of the key structural characteristics responsible for the robust performance of this MION formulation can be exploited for future applications and development
or materials in this article to specify adequately the experimental procedure
In no case does such identification imply recommendation or endorsement by the National Institute of Standards and Technology
nor does it imply that the materials or equipment identified are necessarily the best available for the purpose
tetrakis (hydroxymethyl) phosphonium chloride (THPC)
potassium carbonate and chloroauric acid tetrahydrate (HAuCl4.4H2O) were obtained from Sigma-Aldrich
Ammonium hydroxide solution (30%) was purchased from Merck Company
All the reagents were analytical grade and used as received
2 mL) were added to 90 mL of deionized water and stirred rapidly for ten minutes
3.4 mL) was quickly added and the solution immediately turned dark brown
JHU MIONs were coated with silica using a modified Stöber method<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 52" title="Stöber, W., Fink, A. &amp; Bohn, E. Controlled growth of monodisperse silica spheres in micron size range. J. Colloid Interf. Sci. 26, 62–68 (1968)." href="/articles/s41598-018-29711-0#ref-CR52" id="ref-link-section-d317875232e1856">52</a>
JHU MIONs and 30% ammonium hydroxide were added consecutively to a solution of ethanol and water
The nanoparticle mixture was sonicated for 15 minutes followed by addition of TEOS and the flask was placed on a mechanical rocker overnight
The silica-coated particles were washed three times with ethanol by centrifugation to remove excess TEOS
and the solution was mixed overnight on a rocker
Amino-terminated nanoparticles were washed three times in ethanol by centrifugation
The silica surface was seeded with the gold THPC colloid suspension (See Supporting Information)
The THPC precursor solution was diluted with aqueous K2CO3 and sonicated for two minutes
1 M (molL−1) and amino-terminated nanoparticles were added to the solution and sonication continued for two minutes
Gold seeded nanoparticles were washed once by centrifugation with aqueous K2CO3 and three times using a permanent magnet
The particles were redistributed in aqueous K2CO3
followed by addition of 1% HAuCl4 solution
The solution was mixed by vortexing for 30 min and hydroxylamine (50% in H2O) was added
The mixture immediately turned dark purple
The nanoparticles were washed three times with aqueous K2CO3 using a permanent magnet
resuspended in aqueous K2CO3 and stored at 4 °C
A summary of samples prepared and characterization performed is provided in Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/articles/s41598-018-29711-0#Tab1">1</a>
A refractive index of 1.33 (Fe3O4) and 2.42 for DI water were used
Note that images shown were taken of individual nanoparticles well separated from any large clusters
Unpolarized SANS data were acquired on the CHRNS 30 m SANS (NG7) instrument at the National Institute of Standards and Technology Center for Neutron Research (NCNR) in Gaithersburg
Neutron wavelength was 0.84 nm in transmission
Instrument configurations enabled measurements having scattering vectors (Q) from 3 × 10−5 to 5 × 10−1 Å−1 using three detector settings (15 m
Samples were measured in water (H2O) at room temperature
which was accomplished using SasView (Supplemental Information)
Model fitting was constrained using data from other measurements
DLS and by combining known material properties
the models were correlated between samples by using the parameters determined in the previous model (e.g.
using the JHU-MIONs crystallite sizes in the Si-MIONs fits)
so that subsequent models were constrained by the earlier results
Images were reconstructed and analyzed with ImageJ (NIH
To assess the MR contrast capabilities of MIONs 1
phantoms ranging in iron concentration from 0–80 μg/ml (0–1.4 mM) were imaged
The graph inset shows iron concentration (mM) plotted versus the inverse of T2
The trendline slopes for each nanoparticle give R2
which is a measure of nanoparticle contrast efficiency
Following CT imaging and/or AMF hyperthermia therapy
mice were sacrificed and tumors were excised
Tumors were fixed for at least 48 hours in 10% formalin solution before being embedded in paraffin
The paraffin blocks were sectioned and stained with hematoxylin and eosin (H&amp;E)
H&amp;E and Prussian blue staining were performed by the Molecular &amp; Comparative Pathobiology Histology Core at Johns Hopkins Medical Institute
The silver enhancement kit was used according to the kit instructions (BBI Solutions
The histological sections were examined under an Eclipse 80i microscope (Nikon Instruments
Whole-slice images were assembled from multiple images obtained at 4x magnification
Magnified images were obtained with a 20X objective
Heating rates of JHU MIONs and AuSi-MIONs via laser excitation were compared in solution using a 5.5 W (780 nm) laparoscopic laser directed at the nanoparticle solutions
The increases in temperature were monitored using a FLIR thermal imaging camera and SARs were normalized based on iron content
X-ray computed tomography (CT) imaging was performed on gel samples loaded with nanoparticle concentrations ranging 0–7 mg Fe/ml
CT imaging was performed at 65 kV and 0.7 mA with a SARRP (xStrahl Ltd.
Images were reconstructed using 1800 projections and Hounsfield units were calculated for each nanoparticle concentration with ImageJ software
Anticancer drug delivery: an update on clinically applied nanotherapeutics
Critical review on the toxicity of some widely used engineered nanoparticles
Multifunctional magnetic nanoparticles for targeted imaging and therapy
Small is smarter: Nano MRI contrast agents – advantages and recent achievements
Ferumoxytol In Iron Deficiency Anaemia in Adults With Chronic Kidney Disease
Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combine with external beam radiotherapy on patients with recurrent glioblastoma multiforme
Physics of heat generation using magnetic nanoparticles for hyperthermia
Morbidity and quality of life during thermotherapy using magnetic nanoparticles in locally recurrent prostate cancer: Results of a prospective phase I trial
Thermotherapy of prostate cancer using magnetic nanoparticles: Feasibility
and three-dimensional temperature distribution
Magnetic nanoparticle hyperthermia enhances radiation therapy: A study in mouse models of human prostate cancer
Magnetic fluid hyperthermia for bladder cancer: A preclinical dosimetry study
Thermal dosimetry predictive of efficacy of 111In-ChL6 nanoparticle AMF-induced thermoablative therapy for human breast cancer in mice
Development of tumor targeting bioprobes (111In-chimeric L6 monoclonal antibody nanoparticles) for alternating magnetic field cancer therapy
Development of intraarterial hyperthermia using a dextran-magnetite complex
Targeted hyperthermia using dextran magnetite complex: A new treatment modality for liver tumors
Targeting liver tumors with hyperthermia: Ferromagnetic embolization in a rabbit liver tumor model
The effect of tumour size on ferromagnetic embolization hyperthermia in a rabbit liver tumour model
Arterial embolization hyperthermia: hepatic iron particle distribution and its poteintial determination by magnetic resonance imaging
Image-guided thermal therapy with a dual-contrast magnetic nanoparticle formulation: A feasibility study
Intra-arterial therapies for hepatocellular carcinomas: Where do we stand
Gold and iron oxide hybrid nanocomposite materials
Imaging and drug delivery using theranostic nanoparticles
Design strategies of hybrid metallic nanoparticles for theragnostic applications
Inorganic nanocrystals as contrast agents in MRI: synthesis
coating and introduction of multifunctionality
Nano-magnetic particles used in biomedicine: Core and coating materials
Composite magnetic-plasmonic nanoparticles for biomedicine: Manipulation and imaging
Internal magnetic structure of nanoparticles dominates time-dependent relaxation processes in a magnetic field
Iron Oxides in the Laboratory: Preparation and Characterization
Bifunctional gold nanoshells with a superparamagnetic iron oxide-silica core suitable for both MR imaging and photothermal therapy
Au/Polypyrrole@Fe3O4 nanocomposites for MR/CT dual-modal imaging guided-photothermal therapy: An in vitro study
Nanoshells with targete simultaneous enhancement of magnetic and optical imaging and photothermal therapeutic response
Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy
Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles
Synthesis and testing of modular dual-modality nanoparticles for magnetic resonance and multispectral photoacoustic imaging
Preparation of high-concentration colloidal solution of silica-coated gold nanoparticles and their application to X-ray imaging
Synthesis of AU-Fe3O4 heterostructured nanoparticles for in vivo computed tomography and magnetic resonance dual model imaging
Synthesis and application of strawberry-like Fe3O4-Au nanoparticles as CT-MR dual-modality contrast agents in accurate detection of the progressive liver disease
Dendrimer-assisted formation of Fe3O4/Au nanocomposite particles for targeted dual mode CT/MR imaging of tumors
Gold-coated iron nanoparticles for biomedical applications
Engineered theranostic magnetic nanostructures: Role of composition and surface cotatin on magnetic resonance imaging contrast and thermal activation
Ascorbic acid-mediated synthesis and characterization of iron oxide/gold core-shell nanoparticles
Fabrication and dispersion of gold-shell-protected magnetite nanoparticles: Systematic control using polyethyleneimine
Structured and magnetic properties of gold and silica doubly coated γ-Fe2O3 nanoparticles
Bifunctional gold-coated magnetic silica spheres
New iron-oxide particles for magnetic nanoparticle hyperthermia: An in-vitro and in-vivo pilot study
Proc SPIE 8584 Energy-Based Treatment of Tissue and Assessment VII 8584
Magnetic resonance imaging contrast of iron oxide nanoparticles developed for hyperthermia is dominated by iron content
Engineering of drug nanoparticles by HGCP for pharmaceutical applications
The 30 m Small-Angle Neutron Scattering Instruments at the National Institute of Standards and Technology
Controlled growth of monodisperse silica spheres in micron size range
Reduction and analysis of SANS and USANS data using IGOR Pro
Application of high amplitude alternating magnetic fields for heat induction of nanoparticles localized in cancer
Magnetic nanoparticle heating efficiency reveals magneto-structural differences when characterized with a wide ranging and high amplitude alternating magnetic field
Localized surface plasmon resonance spectroscopy and sensing
Plasmonic photothermal therapy (PPTT) using gold nanoparticles
Method to reduce non-specific heating of small animals in solenoid coils
Characterization and optimization of gold nanoparticle-based silver-enhanced immunoassays
An optimised spectrophotometric assay for convenient and accurate quantitation of intracellular iron from iron oxide nanoparticles
NIST Center for Neutron Research, SANS &amp; USANS data reduction and analysis online tools, <a href="http://ncnr.nist.gov/programs/sans/data/red_anal.html" data-track="click_references" data-track-action="external reference" data-track-value="external reference" data-track-label="http://ncnr.nist.gov/programs/sans/data/red_anal.html">http://ncnr.nist.gov/programs/sans/data/red_anal.html</a>
Modified solenoid coil that efficiently produces high amplitude AC magnetic fields with enhanced uniformity for biomedical applications
Calibration of a quasi-adiabatic magneto-thermal calorimeter used to characterize magnetic nanoparticle heating
Experimental estimation and analysis of variance of the measured loss power of magnetic nanoparticles
Guide for the Care and Use of Laboratory Animals 7th ed
small animal radiation research platform with x-ray tomographic guidance capabilities
Nearly complete regression of tumors via collective behavior of magnetic nanoparticles in hyperthermia
<a data-track="click" data-track-action="download citation references" data-track-label="link" rel="nofollow" href="https://citation-needed.springer.com/v2/references/10.1038/s41598-018-29711-0?format=refman&amp;flavour=references">Download references</a>
Gagnon for assistance with SANS measurements
Research reported in this manuscript was supported by: the National Cancer Institute of the National Institutes of Health under Award Numbers P30CA006973 and T32-CA130840
the Safeway Foundation/Prostate Cancer Foundation
the National Science Foundation under agreement DMR-0944772 and Mr
This work benefited from the use of the SasView application
originally developed under NSF award DMR-0520547
SasView contains code developed with funding from the European Union’s Horizon 2020 research and innovation programme under the SINE2020 project
Present address: Department of Mechanical Engineering
Department of Radiation Oncology and Molecular Radiation Sciences
Johns Hopkins University School of Medicine
Department of Materials Science and Engineering
Morgan Department of Radiology and Radiological Sciences
synthesized and characterized the nanoparticles
conducted SANS experiments and data analysis
performed animal imaging and heating experiments
are inventors on issued and pending nanoparticle patents
All patents are assigned to Johns Hopkins University or Aduro Biotech
Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations
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MION in a blue dress holds her signature electric guitar
Singer-songwriter MION has just completed all May shows as part of her European tour
She has since announced the dates for the month of June
 After the kick-off of the European tour at the Dutch convention Heroes Made in Asia
MION has been travelling around from the Netherlands to Portugal
she will start from her current home base United Kingdom with shows at two events
Leeds Anime &amp; Gaming Con and Japan Fest
then travel to Spain for a weekend at Madrid Otaku
to Sweden for the first edition of Heroes Made in Asia Stockholm and ends the month in Italy at COMICON
In the last year, the singer-songwriter has focused on shows in the United Kingdom as she currently lives there currently and for 2023 her plans of going further into Europe succeeded with the many shows that she has done and will do. The singer-songwriter will perform in at least 10 different countries this spring and summer. Keep an eye on MION’s <a href="https://www.mionjp.com/schedule" target="_blank" rel="noopener">official website</a> for more information
MION has been active as a singer-songwriter for more than 10 years and has released more than 10 solo singles
Besides her various shows in home country Japan and the UK
where she has been operating from since 2022
the pop-rock musician has also made appearances in South Korea
MION’s current objectives are to improve as a singer-songwriter and aid in spreading Japanese culture outside of Japan
She also wants to serve as a link between Japanese and European artists
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 © 2012 - 2025 AVO Magazine - One Click Closer to Japan
© 2012 - 2025 AVO Magazine - One Click Closer to Japan
XPO and Schneider Electric have deployed a new multimodal freight solution between France and the UK
The sustainable road-rail combination is the latest innovation in the companies’ longstanding European partnership
is committed to bridging progress and sustainability
Its target is to become carbon-neutral in its operations by 2025
XPO has been a strategic partner to Schneider for 10 years
less-than-truckload and multimodal services in France and Spain
Vice President – Indirect Procurement for Schneider Electric
our growth strategy prioritises innovation and continuous improvement
XPO excels at developing alternative transport solutions that align with our goals
Their new France-to-UK solution has been delivering more efficiency with less environmental impact from day one of the implementation.”
XPO’s bespoke solution for Schneider is managed by proprietary XPO technology and moves parts and components on round-trip runs between Schneider’s warehouse in Mions
XPO’s road fleet transports containers of freight from Mions to the rail terminal in Vénissieux; from there
the containers travel by train through the Eurotunnel or terminate at Dourges
XPO’s road fleet completes the deliveries to Telford
By utilising rail and ferry to cover more than 650 km of the trip
XPO has created additional capacity for Schneider and will reduce carbon emissions by an estimated 46% per year (172 tonnes of CO2)
compared with all-road transport of 200 full truckloads
“Our multimodal corridors are connecting key trade areas in Europe by road
rail and sea in response to customer requests
These solutions deliver cost efficiencies and contribute to the decarbonisation of supply chains
We are strongly committed to alternative transport solutions and will ensure that our valued partnership with Schneider Electric receives the full benefit of our innovation.”
extensive access to capacity and investment in digital freight management have established the company as a leading transport innovator in Western Europe
XPO is known for taking a collaborative approach to customer partnerships and its commitment to sustainable development
     Information05 May 2025  GXO and Blue Yonder announce new strategic global agreement   GXO Logistics and Blue Yonder have announced a global multi-year strategic agreement to deploy new end-to-end logistics software solutions that will e...   <a href="/article/gxo-and-blue-yonder-announce-new-strategic-global-agreement" aria-label="Read more about GXO and Blue Yonder announce new strategic global agreement"> Read More </a> 
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