Phospholipid micelle encapsulated gadolinium oxide nanoparticles for imaging and gene delivery (original) (raw)
Related papers
Current Topics in Medicinal Chemistry, 2013
As we move towards an era of personalized medicine, molecular imaging contrast agents are likely to see an increasing presence in routine clinical practice. Magnetic resonance (MR) imaging has garnered particular interest as a platform for molecular imaging applications due its ability to monitor anatomical changes concomitant with physiologic and molecular changes. One promising new direction in the development of MR contrast agents involves the labeling and/or loading of nanoparticles with gadolinium (Gd). These nanoplatforms are capable of carrying large payloads of Gd, thus providing the requisite sensitivity to detect molecular signatures within disease pathologies. In this review, we discuss some of the progress that has recently been made in the development of Gd-based macromolecules and nanoparticles and outline some of the physical and chemical properties that will be important to incorporate into the next generation of contrast agents, including high Gd chelate stability, high "relaxivity per particle" and "relaxivity density", and biodegradability.
Hybrid Gadolinium Oxide Nanoparticles: Multimodal Contrast Agents for in Vivo Imaging
Journal of the American Chemical Society, 2007
Luminescent hybrid nanoparticles with a paramagnetic Gd2O3 core were applied as contrast agents for both in vivo fluorescence and magnetic resonance imaging. These hybrid particles were obtained by encapsulating Gd 2O3 cores within a polysiloxane shell which carries organic fluorophores and carboxylated PEG covalently tethered to the inorganic network. Longitudinal proton relaxivities of these particles are higher than the positive contrast agents like Gd-DOTA which are commonly used for clinical magnetic resonance imaging. Moreover these particles can be followed up by fluorescence imaging. This study revealed that these particles suited for dual modality imaging freely circulate in the blood vessels without undesirable accumulation in lungs and liver.
POLYMER-MODIFIED GADOLINIUM NANOPARTICLES FOR TARGETED MAGNETIC RESONANCE IMAGING AND THERAPY
Nano LIFE, 2010
Functional imaging is a novel area in radiological sciences and allows for the non-invasive assessment and visualization of speci¯c targets such as gene and protein expression, metabolic rates, and drug delivery in intact living subjects. As such, the¯eld of molecular imaging has been de¯ned as the non-invasive, quantitative, and repetitive imaging of biomolecules and biological processes in living organisms. For example, cancer cells may be genetically altered to attract molecules that alter the magnetic susceptibility, thereby permitting their identi¯cation by 263 magnetic resonance imaging. These contrast agents and/or molecular reporters are seen as essential to the task of molecular medicine to increase both sensitivity and speci¯city of imaging. Therefore, there are¯ve general principles which need to be ful¯lled in order to conduct a successful in vivo molecular imaging study: (1) selection of appropriate cellular and subcellular targets; (2) development of suitable in vivo a±nity ligands (molecular probes); (3) delivery of these probes to the target organ; (4) ampli¯cation strategies able to detect minimal target concentrations; and (5) development of imaging systems with high resolution. Although there has been a wide range of routes taken to incorporate both imaging agents and a disease-targeting moiety into diagnostic devices, arguably the most interesting of these routes employs the use of nanoparticles. Nanoscale diagnostic systems that incorporate molecular targeting agents and diagnostic imaging capabilities are emerging as the next-generation imaging agents and have the potential to dramatically improve the outcome of the imaging, diagnosis, and treatment of a wide range of diseases. The present review addresses chemical aspects in development of molecular probes based upon gadolinium nanoparticles and their potential role in translational clinical imaging and therapy.
Properties Evaluation of a New MRI Contrast Agent Based on Gd-Loaded Nanoparticles
Biological Trace Element Research, 2010
Nanosized materials of gadolinium oxide can provide high-contrast enhancement in magnetic resonance imaging (MRI). The aim of this research was to characterize a novel emulsion composed of a silicon-based nanocomposite polymer (NCP) and gadolinium (III) oxide (Gd 2 O 3 ) nanoparticles. The size and morphological structure of this nanoparticle are determined by particle size analysis device (zeta sizer) and transmission electronic microscope. We determined composition of Gd 2 O 3 nanoparticles with energy dispersive X-ray analysis (EDXA) and magnetic resonance signal by T 1 -weighted MRI. Cytotoxicity of Gd 2 O 3 nanoparticles in SK-MEL-3 cancer cells was evaluated. Zeta sizer showed Gd 2 O 3 nanoparticles to be 75 nm in size. EDXA indicated the two main chemical components of gadolinium-nanocomposite polymer emulsion: gadolinium and silicon and MRI also showed a significantly higher incremental relaxivity for Gd 2 O 3 nanoparticles compared to Magnevist (conventional contrast agent). In such concentrations, the slope of R 1 relaxivity (1/T 1 ) vs. concentration curve of Magnevist and Gd 2 O 3 were 4.33, 7.98 s −1 mM −1 . The slope of R 2 relaxivity (1/T 2 ) vs. concentration curve of Magnevist and Gd 2 O 3 were 5.06, 13.75 s −1 mM −1 . No appreciable toxicity was observed with Gd 2 O 3 nanoparticles. Gadolinium-nanocomposite polymer emulsion is well characterized and has potential as a useful contrast agent for magnetic resonance molecular imaging.
Journal of Nanoscience and Nanotechnology, 2006
In this article, we use a nanotemplate engineering approach to prepare biodegradable nanoparticles composed of FDA-approved materials and possessing accessible gadolinium (Gd) atoms and demonstrate their potential as a Magnetic Resonance Imaging (MRI) contrast agent. Nanoparticles containing dimyristoyl phosphoethanolamine diethylene triamine penta acetate (PE-DTPA) were prepared using 3.5 mg of Brij 78, 2.0 mg of emulsifying wax and 0.5 mg of PE-DTPA/ml from a microemulsion precursor. After the addition of GdCl 3 , the presence of Gd on the surface of nanoparticles was characterized using inductively coupled plasma atomic emission spectroscopy and Scanning Transmission Electron Microscopy (STEM). The in vitro relaxivities of the PE-DTPA-Gd nanoparticles in different media were assessed at different field strengths. The conditional stability constant of Gd binding to the nanoparticles was determined using competitive spectrophotometric titration. Transmetallation kinetics of the gadolinium ion from PE-DTPA-Gd nanoparticles with zinc as the competing ionic was measured using the relaxivity evolution method. Nanoparticles with a diameter of ∼130 nm possessing surface chelating functions were made from GRAS (Generally Regarded As Safe) materials. STEM demonstrated the uniform distribution of Gd 3+ on the surface of the nanoparticles. The thermodynamic binding constant for Gd 3+ to the nanoparticles was ∼10 18 M −1 and transmetallation studies with Zn 2+ yielded kinetic constants K 1 and K −1 of 0.033 and 0.022 1/h, respectively, with an equilibrium constant of 1.5. A payload of ∼10 5 Gd/nanoparticle was achieved; enhanced relaxivities were observed, including a pH dependence of the transverse relaxivity (r 2). Nanoparticles composed of materials that have been demonstrated to be hemocompatible and enzymatically metabolized and possessing accessible Gd ions on their surface induce relaxivities in the bulk water signal that make them potentially useful as next-generation MRI tumor contrast enhancement agents.
International journal of pharmaceutics, 2017
We report water-in-oil microemulsion mediated synthesis of PEG(1) coated Gd2O3 NPs(2) loaded with fluorescent anti-cancer drug dox(3) for synchronous drug delivery, optical and MR(4) imaging applications. These PEG covered Gd2O3 NPs loaded with dox (Gd-PEG-dox NPs) were found to possess spherical morphology with 13nm size as measured from TEM and the hydrodynamic diameter comes out to be 37nm as determined from DLS. Fluorescence spectra and fluorescence microscopy images confirmed optical activity of the NPs. The paramagnetic nature of NPs was affirmed by NMR line broadening effect on the spectrum of surrounding water protons. Therefore, these particles can be efficiently used as CA(5) in MR imaging. In vitro analysis showed significant cellular uptake of particles by A-549 cells. A pH dependent drug release pattern was observed for the NPs. Cell viability assay performed on A-549, PANC-1 and U-87 cancerous cell lines revealed that Gd-PEG-dox NPs are cytotoxic. On the basis of these...
Gadolinium-Loaded Nanoparticles: New Contrast Agents for Magnetic Resonance Imaging
Journal of the American Chemical Society, 2000
We have developed a new class of metal-loaded nanoparticles that have potential as contrast agents for medical imaging. These polymeric materials have a core-shell morphology where the interior is a functionalized polymer, that provides high affinity for a specific metal, and the shell consists of a porous hydrophobic polymer that modulates access to the core. In the present case, the nanoparticles are loaded with Gd 3+ to provide contrast in magnetic resonance (MR) imaging. The Gd 3+-loaded nanoparticles described in this paper have a diameter of 120 nm and are, therefore, small enough to pass easily through the vasculature. These particles have been shown to reduce relaxation times in vitro, and provide excellent contrast when used to image the heart and gastrointestinal tract in a rat animal model.
Nanoscale Research Letters, 2012
Despite its good resolution, magnetic resonance imaging intrinsically has low sensitivity. Recently, contrast agent nanoparticles have been used as sensitivity and contrast enhancer. The aim of this study was to investigate a new controlled synthesis method for gadolinium oxide-based nanoparticle preparation. For this purpose, diethyleneglycol coating of gadolinium oxide (Gd 2 O 3 -DEG) was performed using new supervised polyol route, and small particulate gadolinium oxide (SPGO) PEGylation was obtained with methoxy-polyethylene-glycol-silane (550 and 2,000 Da) coatings as SPGO-mPEG-silane550 and 2,000, respectively. Physicochemical characterization and magnetic properties of these three contrast agents in comparison with conventional Gd-DTPA were verified by dynamic light scattering transmission electron microscopy, Fourier transform infrared spectroscopy, inductively coupled plasma, X-ray diffraction, vibrating sample magnetometer, and the signal intensity and relaxivity measurements were performed using 1.5-T MRI scanner. As a result, the nanoparticle sizes of Gd 2 O 3 -DEG, SPGO-mPEG-silane550, and SPGO-mPEG-silane2000 could be reached to 5.9, 51.3, 194.2 nm, respectively. The image signal intensity and longitudinal (r 1 ) and transverse relaxivity (r 2 ) measurements in different concentrations (0.3 to approximately 2.5 mM), revealed the r 2 /r 1 ratios of 1.13, 0.89, 33.34, and 33.72 for Gd-DTPA, Gd 2 O 3 -DEG, SPGO-mPEG-silane550, and SPGO-mPEG-silane2000, respectively. The achievement of new synthesis route of Gd 2 O 3 -DEG resulted in lower r 2 /r 1 ratio for Gd 2 O 3 -DEG than Gd-DTPA and other previous synthesized methods by this and other groups. The smaller r 2 /r 1 ratios of two PEGylated-SPGO contrast agents in our study in comparison with r 2 /r 1 ratio of previous PEGylation (r 2 /r 1 = 81.9 for mPEG-silane 6,000 MW) showed that these new three introduced contrast agents could potentially be proper contrast enhancers for cellular and molecular MR imaging.
Multifunctional gadolinium oxide nanoparticles: towards image-guided therapy
Imaging in Medicine, 2010
Ultrasmall gadolinium-based nanoparticles (GBNs) induce both a positive contrast for magnetic resonance imaging and a radiosentizing effect. The exploitation of these characteristics leads to a greater increase in lifespan of rats bearing brain tumors since the radiosensitizing effect of GBNs can be activated by X-ray microbeams when the gadolinium content is, at the same time, sufficiently high in the tumor and low in the surrounding healthy tissue. GBNs exhibit therefore an interesting potential for image-guided radiotherapy.
Mémoire ocompatible nanoparticles and gadolinium complexes for MRI plications
2013
Performances of double-emulsion techniques (W/O/W and W/O/O) and ionotropic gelation process were compared to achieve encapsulation of gadolinium MRI contrast agents (GdCAs) into biocompatible polymeric nanoparticles (NPs) with high Gd-loadings. The better approach proved to be ionotropic gelation with H[Gd(DOTA)] as GdCA. Relaxometry evaluation of H[Gd(DOTA)] NPs efficiency demonstrated that incorporation of H[Gd(DOTA)] inside an hydrogel matrix highly improved H[Gd(DOTA)] relaxivity. Particle efficacy as MR contrast agents was further demonstrated on a 3 T clinical imager: a significant improvement of T1and T2MR signals was obtained at doses much lower than the currently used. 2012 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.