5 research outputs found
Complete Exchange of the Hydrophobic Dispersant Shell on Monodisperse Superparamagnetic Iron Oxide Nanoparticles
High-temperature synthesized monodisperse
superparamagnetic iron
oxide nanoparticles are obtained with a strongly bound ligand shell
of oleic acid and its decomposition products. Most applications require
a stable presentation of a defined surface chemistry; therefore, the
native shell has to be completely exchanged for dispersants with irreversible
affinity to the nanoparticle surface. We evaluate by attenuated total
reflectance−Fourier transform infrared spectroscopy (ATR−FTIR)
and thermogravimetric analysis/differential scanning calorimetry (TGA/DSC)
the limitations of commonly used approaches. A mechanism and multiple
exchange scheme that attains the goal of complete and irreversible
ligand replacement on monodisperse nanoparticles of various sizes
is presented. The obtained hydrophobic nanoparticles are ideally suited
for magnetically controlled drug delivery and membrane applications
and for the investigation of fundamental interfacial properties of
ultrasmall core–shell architectures
Individually Stabilized, Superparamagnetic Nanoparticles with Controlled Shell and Size Leading to Exceptional Stealth Properties and High Relaxivities
Superparamagnetic
iron oxide nanoparticles (SPION) have received immense interest for
biomedical applications, with the first clinical application as negative
contrast agent in magnetic resonance imaging (MRI). However, the first
generation MRI contrast agents with dextran-enwrapped, polydisperse
iron oxide nanoparticle clusters are limited to imaging of the liver
and spleen; this is related to their poor colloidal stability in biological
media and inability to evade clearance by the reticuloÂendothelial
system. We investigate the qualitatively different performance of
a new generation of individually PEG-grafted core–shell SPION
in terms of relaxivity and cell uptake and compare them to benchmark
iron oxide contrast agents. These PEG-grafted SPION uniquely enable
relaxivity measurements in aqueous suspension without aggregation
even at 9.4 T magnetic fields due to their extraordinary colloidal
stability. This allows for determination of the size-dependent scaling
of relaxivity, which is shown to follow a <i>d</i><sup>2</sup> dependence for identical core–shell structures. The here
introduced core–shell SPION with ∼15 nm core diameter
yield a higher <i>R</i><sub>2</sub> relaxivity than previous
clinically used contrast agents as well as previous generations of
individually stabilized SPION. The colloidal stability extends to
control over evasion of macrophage clearance and stimulated uptake
by SPION functionalized with protein ligands, which is a key requirement
for targeted MRI
Evaluation of High-Yield Purification Methods on Monodisperse PEG-Grafted Iron Oxide Nanoparticles
Fundamental research
on nanoparticle (NP) interactions and development
of next-generation biomedical NP applications relies on synthesis
of monodisperse, functional, core–shell nanoparticles free
of residual dispersants with truly homogeneous and controlled physical
properties. Still, synthesis and purification of e.g. such superparamagnetic
iron oxide NPs remain a challenge. Comparing the success of different
methods is marred by the sensitivity of analysis methods to the purity
of the product. We synthesize monodisperse, oleic acid (OA)-capped,
Fe<sub>3</sub>O<sub>4</sub> NPs in the superparamagnetic size range
(3–10 nm). Ligand exchange of OA for polyÂ(ethylene glycol)
(PEG) was performed with the PEG irreversibly grafted to the NP surface
by a nitrodopamine (NDA) anchor. Four different methods were investigated
to remove excess ligands and residual OA: membrane centrifugation,
dialysis, size exclusion chromatography, and precipitation combined
with magnetic decantation. Infrared spectroscopy and thermogravimetric
analysis were used to determine the purity of samples after each purification
step. Importantly, only magnetic decantation yielded pure NPs at high
yields with sufficient grafting density for biomedical applications
(∼1 NDA-PEGÂ(5 kDa)/nm<sup>2</sup>, irrespective of size). The
purified NPs withstand challenging tests such as temperature cycling
in serum and long-term storage in biological buffers. Dynamic light
scattering, transmission electron microscopy, and small-angle X-ray
scattering show stability over at least 4 months also in serum. The
successful synthesis and purification route is compatible with any
conceivable functionalization for biomedical or biomaterial applications
of PEGylated Fe<sub>3</sub>O<sub>4</sub> NPs
Interaction of Size-Tailored PEGylated Iron Oxide Nanoparticles with Lipid Membranes and Cells
Targeted nanomedicine
builds on the concept that nanoparticles
can be directed to specific tissues while remaining inert to others
organs. Many studies have been performed on the synthesis and cellular
interactions of core–shell nanoparticles, in which a functional
inorganic core is coated with a biocompatible polymer layer that should
reduce nonspecific uptake and cytotoxicity. However, work is lacking
that relates structural parameters of the core–shell structure
and colloidal properties directly to interactions with cell membranes
and further correlates these interactions to cell uptake. We have
synthesized monodisperse (SD < 10%), single-crystalline, and superparamagnetic
iron oxide nanoparticles (SPION) of different core size (3–8
nm) that are densely grafted with nitrodopamine-polyÂ(ethylene glycol)
(NDA-PEGÂ(5 kDa)) brushes. We investigated the interactions of the
PEGylated SPION with biomimetic membranes and cancer and kidney cells.
It is shown that a dense homogeneous PEG shell suppresses membrane
interactions and cell uptake but that nanoparticle curvature can influence
membrane interactions for similarly grafted nanoparticles. Weak adsorption
to anionic lipid membranes is shown to correlate with eukaryote cell
uptake and is attributed to double-layer interactions without direct
membrane penetration. This attraction is strongly suppressed during
physiological conditions and leads to unprecedented low cell uptake
and full cell viability when compared to those of traditional dextran-coated
SPION. Less curved (larger core) PEGylated SPION show weaker membrane
adsorption and lower cell uptake due to effectively denser shells.
These results provide a better understanding of design criteria for
core–shell nanoparticles in terms of avoiding nonspecific uptake
by cells, reducing toxicity, and increasing circulation time
Doping Method Determines Para- or Superparamagnetic Properties of Photostable and Surface-Modifiable Quantum Dots for Multimodal Bioimaging
Semiconductor
quantum dots (QDs) are widely used for optical applications
and bioimaging. In comparison to organic dyes used for fluorescent
labeling, QDs exhibit very high photostability and can be further
surface modified. Equipping QDs with magnetic properties (mQDs) makes
it possible to combine fluorescence and magnetic resonance imaging
analyses. For this purpose, we have prepared water-dispersible and
magnetic CdTe/ZnS mQDs, whereby ferrous ions are selectively incorporated
in either their cores or their shells. This study aims at understanding
the differences in optical, structural, and magnetic properties between
these core- and shell-doped mQDs. Field-dependent isothermal magnetic
susceptibility measurements show that shell-doped mQDs exhibit paramagnetic
and their core-doped equivalents superÂparamagnetic behavior
near room temperature. Shell doping results in about 1.7 times higher
photoluminescence quantum yields and 1.4 times higher doping efficiency
than core doping. X-ray diffraction patterns reveal that core doping
leads to defects in the lattice and hence to a severe decrease in
crystallinity, whereas shell doping has no significant impact on the
crystal structure and consequently fewer disadvantages regarding the
mQD’s quantum yield. These selective doping approaches, particularly
shell doping, allow for the tailored design of paramagnetic QDs having
modifiable and biocompatible particle surfaces. The organic ligandsî—¸in
this study <i>N</i>-acetyl-l-cysteineî—¸sufficiently
prevent leakage of toxic metal ions, as shown by cytotoxicity assays
with HepG2 cells. Confocal laser scanning microscopy shows that mQDs
are internalized by these cells and accumulated near their nuclei.
This study shows that biocompatible, fluorescent, and paramagnetic
QDs are promising photostable labels for multimodal bioimaging