6 research outputs found
Conformational Changes in High-Density Lipoprotein Nanoparticles Induced by High Payloads of Paramagnetic Lipids
High-density lipoprotein (HDL) nanoparticles
doped with gadolinium
lipids can be used as magnetic resonance imaging diagnostic agents
for atherosclerosis. In this study, HDL nanoparticles with different
molar fractions of gadolinium lipids (0 < <i>x</i><sub>Gd‑lipids</sub> < 0.33) were prepared, and the MR relaxivity
values (<i>r</i>1 and <i>r</i>2) for all compositions
were measured. Both <i>r</i>1 and <i>r</i>2 parameters
reached a maximal value at a molar fraction of approximately <i>x</i><sub>Gd‑lipids</sub> = 0.2. Higher payloads of gadolinium
did not significantly increase relaxivity values but induced changes
in the structure of HDL, increasing the size of the particles from <i>d</i><sub>H</sub> = 8.2 ± 1.6 to 51.7 ± 7.3 nm. High
payloads of gadolinium lipids trigger conformational changes in HDL,
with potential effects on the in vivo behavior of the nanoparticles
Mass Production and Size Control of Lipid–Polymer Hybrid Nanoparticles through Controlled Microvortices
Lipid–polymer hybrid (LPH) nanoparticles can deliver
a wide
range of therapeutic compounds in a controlled manner. LPH nanoparticle
syntheses using microfluidics improve the mixing process but are restricted
by a low throughput. In this study, we present a pattern-tunable microvortex
platform that allows mass production and size control of LPH nanoparticles
with superior reproducibility and homogeneity. We demonstrate that
by varying flow rates (i.e., Reynolds number (30–150)) we can
control the nanoparticle size (30–170 nm) with high productivity
(∼3 g/hour) and low polydispersity (∼0.1). Our approach
may contribute to efficient development and optimization of a wide
range of multicomponent nanoparticles for medical imaging and drug
delivery
The Complex Fate in Plasma of Gadolinium Incorporated into High-Density Lipoproteins Used for Magnetic Imaging of Atherosclerotic Plaques
We have previously reported enhancing
the imaging of atherosclerotic
plaques in mice using reconstituted high density lipoproteins (HDL)
as nanocarriers for the MRI contrast agent gadolinium (Gd). This study
focuses on the underlying mechanisms of Gd delivery to atherosclerotic
plaques. HDL, LDL, and VLDL particles containing Gd chelated to phosphatidyl
ethanolamine (DTPA-DMPE) and a lipidic fluorophore were used to demonstrate
the transfer of Gd-phospholipids among plasma lipoproteins <i>in vitro</i> and <i>in vivo</i>. To determine the
basis of this transfer, the roles of phospholipid transfer protein
(PLTP) and lipoprotein lipase (LpL) in mediating the migration of
Gd-DTPA-DMPE among lipoproteins were investigated. The results indicated
that neither was an important factor, suggesting that spontaneous
transfer of Gd-DTPA-DMPE was the most probable mechanism. Finally,
two independent mouse models were used to quantify the relative contributions
of HDL and LDL reconstituted with Gd-DTPA-DMPE to plaque imaging enhancement
by MR. Both sets of results suggested that Gd-DTPA-DMPE originally
associated with LDL was about twice as effective as that injected
in the form of Gd-HDL, and that some of Gd-HDL’s effectiveness <i>in vivo</i> is indirect through transfer of the imaging agent
to LDL. In conclusion, the fate of Gd-DTPA-DMPE associated with a
particular type of lipoprotein is complex, and includes its transfer
to other lipoprotein species that are then cleared from the plasma
into tissues
Nanoclusters of Iron Oxide: Effect of Core Composition on Structure, Biocompatibility, and Cell Labeling Efficacy
Inorganic nanocrystals have a variety of applications
in medicine.
They may serve as contrast agents, therapeutics, and for in vitro
diagnostics. Frequently, the synthesis route yields hydrophobically
capped nanocrystals, which necessitates their subsequent coating to
render a water-soluble and biocompatible probe. Biocompatibility is
crucial for cellular imaging applications, which require large quantities
of diagnostically active nanoparticles to be loaded into cells. We
have previously reported the design and synthesis of a fluorescent
and magnetic resonance imaging-detectable core–shell nanoparticle
that encapsulates hydrophobically coated iron oxide nanocrystals.
The core of soybean oil and iron oxide is covered by a shell mixture
of phospholipids, some of which contained polyethylene glycol. Despite
the biocompatibility of these components, we hypothesize that we can
improve this formulation with respect to <i>in vitro</i> toxicity. To this aim, we measured the effect of six different core
compositions on nanoparticle structure, cell labeling efficacy, and
cell viability, as well as cell tracking potential. We methodically
investigated the causes of toxicity and conclude that, even when combining
biocompatible materials, the resulting formulation is not guaranteed
to be biocompatible
Single Step Reconstitution of Multifunctional High-Density Lipoprotein-Derived Nanomaterials Using Microfluidics
High-density lipoprotein (HDL) is a natural nanoparticle that transports peripheral cholesterol to the liver. Reconstituted high-density lipoprotein (rHDL) exhibits antiatherothrombotic properties and is being considered as a natural treatment for cardiovascular diseases. Furthermore, HDL nanoparticle platforms have been created for targeted delivery of therapeutic and diagnostic agents. The current methods for HDL reconstitution involve lengthy procedures that are challenging to scale up. A central need in the synthesis of rHDL, and multifunctional nanomaterials in general, is to establish large-scale production of reproducible and homogeneous batches in a simple and efficient fashion. Here, we present a large-scale microfluidics-based manufacturing method for single-step synthesis of HDL-mimicking nanomaterials (μHDL). μHDL is shown to have the same properties (<i>e.g.</i>, size, morphology, bioactivity) as conventionally reconstituted HDL and native HDL. In addition, we were able to incorporate simvastatin (a hydrophobic drug) into μHDL, as well as gold, iron oxide, quantum dot nanocrystals or fluorophores to enable its detection by computed tomography (CT), magnetic resonance imaging (MRI), or fluorescence microscopy, respectively. Our approach may contribute to effective development and optimization of lipoprotein-based nanomaterials for medical imaging and drug delivery
Synthesis of Polymer–Lipid Nanoparticles for Image-Guided Delivery of Dual Modality Therapy
For advanced treatment of diseases
such as cancer, multicomponent,
multifunctional nanoparticles hold great promise. In the current study
we report the synthesis of a complex nanoparticle (NP) system with
dual drug loading as well as diagnostic properties. To that aim we
present a methodology where chemically modified poly(lactic-<i>co</i>-glycolic) acid (PLGA) polymer is formulated into a polymer–lipid
NP that contains a cytotoxic drug doxorubicin (DOX) in the polymeric
core and an anti-angiogenic drug sorafenib (SRF) in the lipidic corona.
The NP core also contains gold nanocrystals (AuNCs) for imaging purposes
and cyclodextrin molecules to maximize the DOX encapsulation in the
NP core. In addition, a near-infrared (NIR) Cy7 dye was incorporated
in the coating. To fabricate the NP we used a microfluidics-based
technique that offers unique NP synthesis conditions, which allowed
for encapsulation and fine-tuning of optimal ratios of all the NP
components. NP phantoms could be visualized with computed tomography
(CT) and near-infrared (NIR) fluorescence imaging. We observed timed
release of the encapsulated drugs, with fast release of the corona
drug SRF and delayed release of a core drug DOX. In tumor bearing
mice intravenously administered NPs were found to accumulate at the
tumor site by fluorescence imaging