Biocompatible Contrast Research Articles

Magnetic iron nanoparticles for in vivo targeted delivery and as biocompatible contrast agents

Iron nanoparticles (NPs) of size less than 20 nm were synthesized using an in-house developed cryomill.

Porous silicon nanoparticles as biocompatible contrast agents for magnetic resonance imaging

We propose porous silicon nanoparticles (PSi NPs) with natural oxide coating as biocompatible and bioresorbable contrast agents for magnetic resonant imaging (MRI). A strong shortening of the transversal proton relaxation time (T2) was observed for aqueous suspensions of PSi NPs, whereas the longitudinal relaxation time (T1) changed moderately. The longitudinal and transversal relaxivities are estimated to be 0.03 and 0.4 l/(g·s), respectively, which are promising for biomedical studies. The proton relaxation is suggested to undergo via the magnetic dipole-dipole interaction with Si dangling bonds on surfaces of PSi NPs. MRI experiments with phantoms have revealed the remarkable contrasting properties of PSi NPs for medical diagnostics.

T₁-MRI Fluorescent Iron Oxide Nanoparticles by Microwave Assisted Synthesis.

Iron oxide nanoparticles have long been studied as a T2 contrast agent in MRI due to their superparamagnetic behavior. T1-based positive contrast, being much more favorable for clinical application due to brighter and more accurate signaling is, however, still limited to gadolinium- or manganese-based imaging tools. Though being the only available commercial positive-contrast agents, they lack an efficient argument when it comes to biological toxicity and their circulatory half-life in blood. The need arises to design a biocompatible contrast agent with a scope for easy surface functionalization for long circulation in blood and/or targeted imaging. We hereby propose an extremely fast microwave synthesis for fluorescein-labeled extremely-small iron oxide nanoparticles (fdIONP), in a single step, as a viable tool for cell labeling and T1-MRI. We demonstrate the capabilities of such an approach through high-quality magnetic resonance angiographic images of mice.

Magnetosomes, biogenic magnetic nanomaterials for brain molecular imaging with 17.2 T MRI scanner.

The fast development of sensitive molecular diagnostic tools is currently paving the way for a personalized medicine. A new class of ultrasensitive magnetic resonance imaging (MRI) T₂-contrast agents based on magnetosomes, magnetite nanocrystals biomineralized by magnetotactic bacteria, is proposed here. The contrast agents can be injected into the blood circulation and detected in the picomolar range. Purified magnetosomes are water-dispersible and stable within physiological conditions and exhibit at 17.2 T a transverse relaxivity r₂ four times higher than commercial ferumoxide. The subsequent gain in sensitivity by T₂(*) -weighted imaging at 17.2 T of the mouse brain vasculature is evidenced in vivo after tail vein injection of magnetosomes representing a low dose of iron (20 μmoliron kg(-1)), whereas no such phenomenon with the same dose of ferumoxide is observed. Preclinical studies of human pathologies in animal models will benefit from the combination of high magnetic field MRI with sensitive, low dose, easy-to-produce biocompatible contrast agents derived from bacterial magnetosomes.

2, 3-Dimercaptosuccinic Acid-Modified Iron Oxide Clusters for Magnetic Resonance Imaging

Over the last decade, various magnetic nanomaterials have been developed as magnetic resonance imaging (MRI) contrast agents; the greatest challenges encountered for clinical application have been insufficient stability. In this paper, a lyophilization method for 2, 3-dimercaptosuccinic acid-modified iron oxide (γ-Fe2 O3 @DMSA) nanoparticles was developed to simultaneously overcome two disadvantages; these include insufficient stability and low-magnetic response. After lyophilization, the clusters of γ-Fe2 O3 @DMSA with the size of 156.7 ± 15.3 nm were formed, and the stability of the lyophilized powder (γ-Fe2 O3 @DMSA-LP) increased up to over 3 years. It was also found that rehydrated γ-Fe2 O3 @DMSA-LP could be ingested by RAW264.7 cells in very large quantities. Results of pharmacokinetics and biodistribution studies in vivo indicated that γ-Fe2 O3 @DMSA-LP is a promising liver-targeted material. Furthermore, it also exhibited higher MRI efficiency and longer imaging time in the liver than the well-known product Feridex(®) . Moreover, results of vascular irritation and long-term toxicity experiments demonstrated γ-Fe2 O3 @DMSA-LP could be a nontoxic, biocompatible contrast agent in vivo. Therefore, the proposed γ-Fe2 O3 @DMSA-LP can be used as a potential MRI contrast agent in clinic for hepatic diseases.

Graphene oxide-gadolinium (III) oxide nanoparticle composite: a novel MR contrast agent with high longitudinal and transverse relaxivity

Production of bio-compatible contrast agent materials to enhance the sensitivity of the magnetic resonance imaging (MRI) technique is a highly active area in MRI related research. This work illustrates the potential of a new material: graphene oxide-gadolinium (III) oxide nanoparticle (GO-Gd2O3) composite in yielding both transverse (16.3 mM−1 s−1) and longitudinal relaxivity (40 mM−1 s−1) values which are significantly higher than the proton relaxivity values achieved using the gadolinium based contrast agents currently used in MRI. Such high proton relaxivity values can facilitate low dosage of GO-Gd2O3 composite for obtaining both T1 and T2 weighted high signal-to-noise ratio images in MRI.

In vivo quantitative NMR imaging of fruit tissues during growth using Spoiled Gradient Echo sequence

Nondestructive studies of physiological processes in agronomic products require increasingly higher spatial and temporal resolutions. Nuclear Magnetic Resonance (NMR) imaging is a non-invasive technique providing physiological and morphological information on biological tissues. The aim of this study was to design a robust and accurate quantitative measurement method based on NMR imaging combined with contrast agent (CA) for mapping and quantifying water transport in growing cherry tomato fruits. A multiple flip-angle Spoiled Gradient Echo (SGE) imaging sequence was used to evaluate the intrinsic parameters maps M0 and T1 of the fruit tissues. Water transport and paths flow were monitored using Gd3+/[Fe(CN)6]3−/D−mannitol nanoparticles as a tracer. This dynamic study was carried out using a compartmental modeling. The CA was preferentially accumulated in the surrounding tissues of columella and in the seed envelopes. The total quantities and the average volume flow of water estimated are: 198mg, 1.76mm3/h for the columella and 326mg, 2.91mm3/h for the seed envelopes. We demonstrate in this paper that the NMR imaging technique coupled with efficient and biocompatible CA in physiological medium has the potential to become a major tool in plant physiology research.

PEGylated Gold Nanoparticles as a Biocompatible Contrast Agent in X-ray Imaging of Breast Tumor in Mouse Model

Objective: Though biopsy is ultimately the gold standard for breast cancer detection, medical imaging can be a valuable tool for gathering information in vivo for both screening and diagnosis. In this study, we propose the use of gold nanoparticles (GNPs) modified with polyethylene glycol (PEG) as a biocompatible contrast agent in X- ray imaging of breast cancer in mouse model. . Methods: Gold nanoparticles in spherical shape were coated with PEG and the interaction was investigated by UV/vis spectroscopy. The UV/vis analysis was performed to check the stability of PEG-GNPs complex in human blood serum. The biodistribution and X–ray imaging studies were performed to evaluate the localization of PEGylated GNPs in xenografted breast tumor in mouse model. Results: The interaction of PEG with GNPs was confirmed by UV–vis spectroscopy. The stability of PEG-GNPs was found high at human blood serum with no aggregation. The biodistribution study showed the accumulation of PEGylated GNPs in the site of tumor. The tumor was properly visualized in X-ray images in mouse model. Conclusions: The results showed the potential of PEGylated gold nanoparticles as a contrast agent for X-ray imaging of breast cancer in humans that needs further investigations.

O058 Controlled Nucleation from Gas Supersaturated Solutions, A Novel Bio-compatible Echo Contrast Agent

R A L A B 11⁄448vs47, 21⁄430vs53, 31⁄414vs3, 41⁄413vs2 respectively. Wilcoxon matched-pairs rank sign test was performed, showing a significant ranking difference (improvement) pre & post contrast (p1⁄40.003). GEBDSI for UE TTE was 1.92 0.16 and for CE TTE 1.62 0.11 (p1⁄40.06). Combined endocardial length (RV free wall+RV septum) showed a significant difference (p<0.0001) between UE (35.9 2.0 mm) and CE imaging (51.3 1.3 mm).

Nonpolymeric Surface–Coated Iron Oxide Nanoparticles for In Vivo Molecular Imaging: Biodegradation, Biocompatibility, and Multiplatform

A new approach to the surface engineering of superparamagnetic iron oxide nanoparticles (SPIONs) may encourage their development for clinical use. In this study, we demonstrated that nonpolymeric surface modification of SPIONs has the potential to be an advanced biocompatible contrast agent for biomedical applications, including diagnostic imaging in vivo. Adenosine triphosphate (ATP), which is an innate biomaterial derived from the body, was coated onto the surface of SPIONs. An in vivo degradation study of ATP-coated SPIONs (ATP@SPIONs) was performed for 28 d. To diminish phagocytosis, ATP@SPIONs were surface-modified with gluconic acid. We next studied the ability of the SPIONs to serve as a specific targeted contrast agent after conjugation of cMet-binding peptide. The SPIONs were conjugated with Cy5.5 and labeled with (125)I for multimodality imaging. In vivo and in vitro tumor-targeted binding studies were performed on U87MG cells or a U87MG tumor model using animal SPECT/CT, an optical imaging system, and a 1.5-T clinical MR scanner. ATP@SPIONs showed rapid degradation in vivo and in vitro, compared with ferumoxides. ATP@SPIONs modified with gluconic acid reduced phagocytic uptake, showed improved biodistribution, and provided good targetability in vivo. The gluconic acid-conjugated ATP@SPIONs, when conjugated with cMet-binding peptide, were successfully visualized on the U87MG tumors implanted in mice via multimodality imaging. We suggest that ATP@SPIONs can be used as a multiplatform to target a region of interest in molecular imaging. When we consider the biocompatibility of contrast agents in vivo, ATP@SPIONs are superior to polymeric surface-modified SPIONs.

Potential Nanotoxicity of Pegylated Gold Nanorods having Different Sizes and Shapes as a Biocompatible Contrast Agent for 2PE Imaging

Gold nanoparticles (AuNPs) entices the attention last years in nanobiotechnology. Different methodologies were designed to produce AuNPs with tunable sizes and shapes. Gold nanorods (AuNRs) are candidates for different applications including cell imaging, smart drug delivery and photothermal therapy. AuNRs dispersion is characterized by two surface plasmonic resonances referring to the interaction of incident light with the free electrons of the transversal and longitudinal axes atoms. The absorption wavelength of the longitudinal surface plasmonic resonance is highly sensitive to the aspect ratio of the NRs and the medium dielectric resonance. Regarding to these spectacular properties and by tuning the aspect ratio of the NRs, AuNRs can be useful as contrast agent for cell imaging through controlling the wavelength of the excitation light. Here we report about AuNRs with two different aspect ratios, photochemically synthesized using CTAB as cationic surfactant. Functionalization was performed on the NRs surface to exchange cytotoxic CTAB molecules with thio methoxypolyethylene glycol (mPEG-SH). In order to evaluate the cellular uptake of the AuNRs and the potential nanotoxicity we used cell line, namely: HeLa. The viability of the cells after nanorods uptake was evaluated by colorimetric assay to reveal the percentage of dead and apoptotic cells after exposure. Furthermore, due to the fact that oxidative stress is one of the mechanisms responsible of toxicity of nanoparticles, we investigated the levels of reduced gluthation (GSH) of treated versus control cells by using a second colorimetric assay. 2PE microscopy at different laser wavelengths has been used to estimate the effectiveness of AuNRs as contrasting agent for cell imaging. Occasionally, TEM images were acquired for cells after exposure to NRs to quantify NRs inside the cells and in which specific regions.

Silica-coated super paramagnetic iron oxide nanoparticles (SPION) as biocompatible contrast agent in biomedical photoacoustics

In this study, we report for the first time the use of silica-coated superparamagnetic iron oxide nanoparticles (SPION) as contrast agents in biomedical photoacoustic imaging. Using frequency-domain photoacoustic correlation (the photoacoustic radar), we investigated the effects of nanoparticle size, concentration and biological media (e.g. serum, sheep blood) on the photoacoustic response in turbid media. Maximum detection depth and the minimum measurable SPION concentration were determined experimentally. The nanoparticle-induced optical contrast ex vivo in dense muscular tissues (avian pectus and murine quadricept) was evaluated and the strong potential of silica-coated SPION as a possible photoacoustic contrast agents was demonstrated.

New magnetic-resonance-imaging-visible poly(ε-caprolactone)-based polyester for biomedical applications

A great deal of effort has been made since the 1990s to enlarge the field of magnetic resonance imaging. Better tissue contrast, more biocompatible contrast agents and the absence of any radiation for the patient are some of the many advantages of using magnetic resonance imaging (MRI) rather than X-ray technology. But implantable medical devices cannot be visualized by conventional MRI and a tool therefore needs to be developed to rectify this. The synthesis of a new MRI-visible degradable polymer is described by grafting an MR contrast agent (DTPA-Gd) to a non-water-soluble, biocompatible and degradable poly(ε-caprolactone) (PCL). The substitution degree, calculated by 1H nuclear magnetic resonance and inductively coupled plasma-mass spectrometry, is close to 0.5% and proves to be sufficient to provide a strong and clear T1 contrast enhancement. This new MRI-visible polymer was coated onto a commercial mesh for tissue reinforcement using an airbrush system and enabled in vitro MR visualization of the mesh for at least 1year. A stability study of the DTPA-Gd-PCL chelate in phosphate-buffered saline showed that a very low amount of gadolinium was released into the medium over 52weeks, guaranteeing the safety of the device. This study shows that this new MRI-visible polymer has great potential for the MR visualization of implantable medical devices and therefore the post-operative management of patients.

Intracellular bimodal nanoparticles based on quantum dots for high‐field MRI at 21.1 T

Multimodal, biocompatible contrast agents for high magnetic field applications represent a new class of nanomaterials with significant potential for tracking of fluorescence and MR in vitro and vivo. Optimized for high-field MR applications-including biomedical imaging at 21.1 T, the highest magnetic field available for MRI-these nanoparticles capitalize on the improved performance of chelated Dy(3+) with increasing magnetic field coupled to a noncytotoxic Indium Phosphide/Zinc Sulfide (InP/ZnS) quantum dot that provides fluorescence detection, MR responsiveness, and payload delivery. By surface modifying the quantum dot with a cell-penetrating peptide sequence coupled to an MR contrast agent, the bimodal nanomaterial functions as a self-transfecting high-field MR/optical contrast agent for nonspecific intracellular labeling. Fluorescent images confirm sequestration in perinuclear vesicles of labeled cells, with no apparent cytotoxicity. These techniques can be extended to impart cell selectivity or act as a delivery vehicle for genetic or pharmaceutical interventions.

Transmission Electron Microscopy of Lipid Vesicles for Drug Delivery: Comparison between Positive and Negative Staining

Lipid-containing nanostructures, in the form of solid lipid nanoparticles or iron oxide nanoparticles (NPs) coated with a lipid shell, were used as case studies for assessing and optimizing staining for transmission electron microscopy structural and compositional characterization. These systems are of paramount importance as drug delivery systems or as bio-compatible contrast agents. In particular, we have treated the systems with a negative (phospshotungstic acid) or with a positive (osmium tetroxide) staining agent. For iron-oxide NPs coated with the lipid shell, negative staining was more efficient with respect to the positive one. Nevertheless, in particular cases the combination of the two staining procedures provided more complete morphological and compositional characterization of the particles.

All-optical anatomical co-registration for molecular imaging of small animals using dynamic contrast

Optical molecular imaging in small animals harnesses the power of highly specific and biocompatible contrast agents for drug development and disease research1-7. However, the widespread adoption of in vivo optical imaging has been inhibited by its inability to clearly resolve and identify targeted internal organs. Optical tomography8-11 and combined X-ray and micro-computed tomography (micro-CT)12 approaches developed to address this problem are generally expensive, complex or incapable of true anatomical co-registration. Here, we present a remarkably simple all-optical method that can generate co-registered anatomical maps of a mouse's internal organs, while also acquiring in vivo molecular imaging data. The technique uses a time series of images acquired after injection of an inert dye. Differences in the dye's in vivo biodistribution dynamics allow precise delineation and identification of major organs. Such co-registered anatomical maps permit longitudinal organ identification irrespective of repositioning or weight gain, thereby promising greatly improved accuracy and versatility for studies of orthotopic disease, diagnostics and therapies.

Water‐Soluble Dendrimeric Two‐Photon Tracers for In Vivo Imaging

In a (nut)shell: Covalently wrapped in a protecting and solubilizing dendrimeric shell (see picture), an initially hydrophobic two-photon fluorophore becomes a biocompatible contrast agent with strong emission for imaging in vivo by multiphoton microscopy.