2 research outputs found
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
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