5 research outputs found
Tailoring Polymersome Bilayer Permeability Improves Enhanced Permeability and Retention Effect for Bioimaging
Self-assembled nanoparticles conjugated
with various imaging contrast
agents have been used for the detection and imaging of pathologic
tissues. Inadvertently, these nanoparticles undergo fast, dilution-induced
disintegration in circulation and quickly lose their capability to
associate with and image the site of interest. To resolve this challenge,
we hypothesize that decreasing the bilayer permeability of polymersomes
can stabilize their structure, extend their lifetime in circulation,
and hence improve the quality of bioimaging when the polymersome is
coupled with an imaging probe. This hypothesis is examined by using
poly(2-hydroxyethyl-<i>co</i>-octadecyl aspartamide), sequentially
modified with methacrylate groups, to build model polymersomes. The
bilayer permeability of the polymersome is decreased by increasing
the packing density of the bilayer with methacrylate groups and is
further decreased by inducing chemical cross-linking reactions between
the methacrylate groups. The polymersome with decreased bilayer permeability
demonstrates greater particle stability in physiological media and
ultimately can better highlight tumors in mice over 2 days compared
to those with higher bilayer permeability after labeling with a near-infrared
(NIR) fluorescent probe. We envisage that the resulting nanoparticles
will not only improve diagnosis but also further image-guided therapies
Flow-Mediated Stem Cell Labeling with Superparamagnetic Iron Oxide Nanoparticle Clusters
This
study presents a strategy to enhance the uptake of superparamagnetic
iron oxide nanoparticle (SPIO) clusters by manipulating the cellular
mechanical environment. Specifically, stem cells exposed to an orbital
flow ingested almost a 2-fold greater amount of SPIO clusters than
those cultured statically. Improvements in magnetic resonance (MR)
contrast were subsequently achieved for labeled cells in collagen
gels and a mouse model. Overall, this strategy will serve to improve
the efficiency of cell tracking and therapies
Tailoring the Dependency between Rigidity and Water Uptake of a Microfabricated Hydrogel with the Conformational Rigidity of a Polymer Cross-Linker
Many diverse applications utilize
hydrogels as carriers, sensors,
and actuators, and these applications rely on the refined control
of physical properties of the hydrogel, such as elastic modulus and
degree of swelling. Often, hydrogel properties are interdependent;
for example, when elastic modulus is increased, degree of swelling
is decreased. Controlling these inverse dependencies remains a major
barrier for broader hydrogel applications. We hypothesized that polymer
cross-linkers with varied chain flexibility would allow us to tune
the inverse dependency between the elastic modulus and the degree
of swelling of the hydrogels. We examined this hypothesis by using
alginate and poly(acrylic acid) (PAA) modified with a controlled number
of methacrylic groups as model inflexible and flexible cross-linkers,
respectively. Interestingly, the polyacrylamide hydrogel cross-linked
by the inflexible alginate methacrylates exhibited less dependency
between the degree of swelling and the elastic modulus than the hydrogel
cross-linked by flexible PAA methacrylates. This critical role of
the cross-linker’s inflexibility was related to the difference
of the degree of hydrophobic association between polymer cross-linkers,
as confirmed with pyrene probes added in pregel solutions. Furthermore,
hydrogels cross-linked with alginate methacrylates could tune the
projection area of adhered cells by solely altering elastic moduli.
In contrast, gels cross-linked with PAA methacrylates failed to modulate
the cellular adhesion morphology due to a lower, and smaller, elastic
modulus range to be controlled. Overall, the results of this study
will significantly advance the controllability of hydrogel properties
and greatly enhance the performance of hydrogels in various biological
applications
Worm-Like Superparamagnetic Nanoparticle Clusters for Enhanced Adhesion and Magnetic Resonance Relaxivity
Nanosized
bioprobes that can highlight diseased tissue can be powerful
diagnostic tools. However, a major unmet need is a tool with adequate
adhesive properties and contrast-to-dose ratio. To this end, this
study demonstrates that targeted superparamagnetic nanoprobes engineered
to present a worm-like shape and hydrophilic packaging enhance both
adhesion efficiency to target substrates and magnetic resonance (MR)
sensitivity. These nanoprobes were prepared by the controlled self-assembly
of superparamagnetic iron oxide nanoparticles (SPIONs) into worm-like
superstructures using glycogen-like amphiphilic hyperbranched polyglycerols
functionalized with peptides capable of binding to defective vasculature.
The resulting worm-like SPION clusters presented binding affinity
to the target substrate 10-fold higher than that of spherical ones
and T<sub>2</sub> molar MR relaxivity 3.5-fold higher than that of
conventional, single SPIONs. The design principles discovered for
these nanoprobes should be applicable to a range of other diseases
where improved diagnostics are needed
Leukocyte-Mimicking Stem Cell Delivery via in Situ Coating of Cells with a Bioactive Hyperbranched Polyglycerol
Since stem cells
emerged as a new generation of medicine, there
are increasing efforts to deliver stem cells to a target tissue via
intravascular injection. However, the therapeutic stem cells lack
the capacity to detect and adhere to the target tissue. Therefore,
this study presents synthesis of a bioactive hyperbranched polyglycerol
(HPG) that can noninvasively associate with stem cells and further
guide them to target sites, such as inflamed endothelium. The overall
process is analogous to the way in which leukocytes are mobilized
to the injured endothelium