6 research outputs found
Effect of Gold Nanoparticle Size and Coating on Labeling Monocytes for CT Tracking
With advances in cell therapies,
interest in cell tracking techniques
to monitor the migration, localization, and viability of these cells
continues to grow. X-ray computed tomography (CT) is a cornerstone
of medical imaging but has been limited in cell tracking applications
due to its low sensitivity toward contrast media. In this study, we
investigate the role of size and surface functionality of gold nanoparticles
for monocyte uptake to optimize the labeling of these cells for tracking
in CT. We synthesized gold nanoparticles (AuNP) that range from 15
to 150 nm in diameter and examined several capping ligands, generating
44 distinct AuNP formulations. In vitro cytotoxicity and uptake experiments
were performed with the RAW 264.7 monocyte cell line. The majority
of formulations at each size were found to be biocompatible, with
only certain 150 nm PEG functionalized particles reducing viability
at high concentrations. High uptake of AuNP was found using small
capping ligands with distal carboxylic acids (11-MUA and 16-MHA).
Similar uptake values were found with intermediate sizes (50 and 75
nm) of AuNP when coated with 2000 MW polyÂ(ethylene-glycol) carboxylic
acid ligands (PCOOH). Low uptake values were observed with 15, 25,
100, and 150 nm PCOOH AuNP, revealing interplay between size and surface
functionality. Transmission electron microscopy (TEM) and CT performed
on cells revealed similar patterns of high gold uptake for 50 nm PCOOH
and 75 nm PCOOH AuNP. These results demonstrate that highly negatively
charged carboxylic acid coatings for AuNP provide the greatest internalization
of AuNP in monocytes, with a complex dependency on size
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
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 polyÂ(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
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
Nanodisco Balls: Control over Surface <i>versus</i> Core Loading of Diagnostically Active Nanocrystals into Polymer Nanoparticles
Nanoparticles of complex architectures can have unique properties. Self-assembly of spherical nanocrystals is a high yielding route to such systems. In this study, we report the self-assembly of a polymer and nanocrystals into aggregates, where the location of the nanocrystals can be controlled to be either at the surface or in the core. These nanospheres, when surface decorated with nanocrystals, resemble disco balls, thus the term nanodisco balls. We studied the mechanism of this surface loading phenomenon and found it to be Ca<sup>2+</sup> dependent. We also investigated whether excess phospholipids could prevent nanocrystal adherence. We found surface loading to occur with a variety of nanocrystal types including iron oxide nanoparticles, quantum dots, and nanophosphors, as well as sizes (10–30 nm) and shapes. Additionally, surface loading occurred over a range of polymer molecular weights (∼30–3000 kDa) and phospholipid carbon tail length. We also show that nanocrystals remain diagnostically active after loading onto the polymer nanospheres, <i>i.e.</i>, providing contrast in the case of magnetic resonance imaging for iron oxide nanoparticles and fluorescence for quantum dots. Last, we demonstrated that a fluorescently labeled protein model drug can be delivered by surface loaded nanospheres. We present a platform for contrast media delivery, with the unusual feature that the payload can be controllably localized to the core or the surface
Nanodisco Balls: Control over Surface <i>versus</i> Core Loading of Diagnostically Active Nanocrystals into Polymer Nanoparticles
Nanoparticles of complex architectures can have unique properties. Self-assembly of spherical nanocrystals is a high yielding route to such systems. In this study, we report the self-assembly of a polymer and nanocrystals into aggregates, where the location of the nanocrystals can be controlled to be either at the surface or in the core. These nanospheres, when surface decorated with nanocrystals, resemble disco balls, thus the term nanodisco balls. We studied the mechanism of this surface loading phenomenon and found it to be Ca<sup>2+</sup> dependent. We also investigated whether excess phospholipids could prevent nanocrystal adherence. We found surface loading to occur with a variety of nanocrystal types including iron oxide nanoparticles, quantum dots, and nanophosphors, as well as sizes (10–30 nm) and shapes. Additionally, surface loading occurred over a range of polymer molecular weights (∼30–3000 kDa) and phospholipid carbon tail length. We also show that nanocrystals remain diagnostically active after loading onto the polymer nanospheres, <i>i.e.</i>, providing contrast in the case of magnetic resonance imaging for iron oxide nanoparticles and fluorescence for quantum dots. Last, we demonstrated that a fluorescently labeled protein model drug can be delivered by surface loaded nanospheres. We present a platform for contrast media delivery, with the unusual feature that the payload can be controllably localized to the core or the surface