Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gadolinium Metallofullerene-Based Activatable Contrast Agent for Tumor Signal Amplification and Monitoring of Drug Release.

ABSTRACT: Activatable imaging probes are promising to achieve increased signal-to-noise ratio for accurate tumor diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is a noninvasive imaging technique with excellent anatomic spatial resolution and unlimited tissue penetration depth. However, most of the activatable MRI contrast agents suffer from metal ion-associated potential long-term toxicity, which may limit their bioapplications and clinical translation. Herein, an activatable MRI agent with efficient MRI performance and high safety is developed for drug (doxorubicin) loading and tumor signal amplification. The agent is based on pH-responsive polymer and gadolinium metallofullerene (GMF). This GMF-based contrast agent shows high relaxivity and low risk of gadolinium ion release. At physiological pH, both GMF and drug molecules are encapsulated into the hydrophobic core of nanoparticles formed by the pH-responsive polymer and shielded from the aqueous environment, resulting in relatively low longitudinal relativity and slow drug release. However, in acidic tumor microenvironment, the hydrophobic-to-hydrophilic conversion of the pH-responsive polymer leads to amplified MR signal and rapid drug release simultaneously. These results suggest that the prepared activatable MRI contrast agent holds great promise for tumor detection and monitoring of drug release.

SUBMITTER: Wang S

PROVIDER: S-EPMC6472981 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Gadolinium-encapsulating iron oxide nanoprobe as activatable NMR/MRI contrast agent.

Project description:Herein we report a novel gadolinium-encapsulating iron oxide nanoparticle-based activatable NMR/MRI nanoprobe. In our design, Gd-DTPA is encapsulated within the poly(acrylic acid) (PAA) polymer coating of a superparamagnetic iron oxide nanoparticle (IO-PAA), yielding a composite magnetic nanoprobe (IO-PAA-Gd-DTPA) with quenched longitudinal spin-lattice magnetic relaxation (T(1)). Upon release of the Gd-DTPA complex from the nanoprobe's polymeric coating in acidic media, an increase in the T(1) relaxation rate (1/T(1)) of the composite magnetic nanoprobe was observed, indicating a dequenching of the nanoprobe with a corresponding increase in the T(1)-weighted MRI signal. When a folate-conjugated nanoprobe was incubated in HeLa cells, a cancer cell line overexpressing folate receptors, an increase in the 1/T(1) signal was observed. This result suggests that, upon receptor-mediated internalization, the composite magnetic nanoprobe degraded within the cell's lysosome acidic (pH 5.0) environment, resulting in an intracellular release of Gd-DTPA complex with subsequent T(1) activation. In addition, when an anticancer drug (Taxol) was coencapsulated with the Gd-DTPA within the folate receptor targeting composite magnetic nanoprobe, the T(1) activation of the probe coincided with the rate of drug release and corresponding cytotoxic effect in cell culture studies. Taken together, these results suggest that our activatable T(1) nanoagent could be of great importance for the detection of acidic tumors and assessment of drug targeting and release by MRI.

| S-EPMC3429787 | biostudies-literature

Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis.

Project description:Non-invasive detection of caspase-3/7 activity in vivo has provided invaluable predictive information regarding tumor therapeutic efficacy and anti-tumor drug selection. Although a number of caspase-3/7 targeted fluorescence and positron emission tomography (PET) imaging probes have been developed, there is still a lack of gadolinium (Gd)-based magnetic resonance imaging (MRI) probes that enable high spatial resolution detection of caspase-3/7 activity in vivo. Here we employ a self-assembly approach and develop a caspase-3/7 activatable Gd-based MRI probe for monitoring tumor apoptosis in mice. Upon reduction and caspase-3/7 activation, the caspase-sensitive nano-aggregation MR probe (C-SNAM: 1) undergoes biocompatible intramolecular cyclization and subsequent self-assembly into Gd-nanoparticles (GdNPs). This results in enhanced r1 relaxivity-19.0 (post-activation) vs. 10.2 mM-1 s-1 (pre-activation) at 1 T in solution-and prolonged accumulation in chemotherapy-induced apoptotic cells and tumors that express active caspase-3/7. We demonstrate that C-SNAM reports caspase-3/7 activity by generating a significantly brighter T1-weighted MR signal compared to non-treated tumors following intravenous administration of C-SNAM, providing great potential for high-resolution imaging of tumor apoptosis in vivo.

| S-EPMC4241271 | biostudies-literature

Gadolinium Complexes as Contrast Agent for Cellular NMR Spectroscopy.

Project description:Aqua Gd3+ and Gd-DOTA (gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacete) complexes were studied as a contrast agent in cellular NMR (nuclear magnetic resonance) spectroscopy for distinguishing between intracellular and extracellular spaces. The contrast agents for this purpose should provide strong paramagnetic relaxation enhancement and localize in the extracellular space without disturbing biological functions. Cell membrane permeability to Gd complexes was evaluated from the concentrations of gadolinium complexes in the inside and outside of E. coli cells measured by the 1H-NMR relaxation. The site-specific binding of the complexes to E. coli cells was also analyzed by high-resolution solid-state 13C-NMR. The aqua Gd3+ complex did not enhance T1 relaxation in proportion to the amount of added Gd3+. This Gd3+ concentration dependence and the 13C-NMR indicated that its strong cytotoxicity should be due to the binding of the paramagnetic ions to cellular components especially at the lipid membranes. In contrast, Gd-DOTA stayed in the solution states and enhanced relaxation in proportion to the added amount. This agent exhibited strong T1 contrast between the intra- and extracellular spaces by a factor of ten at high concentrations under which the cells were viable over a long experimental time of days. These properties make Gd-DOTA suitable for selectively contrasting the living cellular space in NMR spectroscopy primarily owing to its weak interaction with cellular components.

| S-EPMC7312942 | biostudies-literature

Gadolinium-based MRI contrast agent for the detection of tyrosinase.

Project description:Tyrosinase is a key enzyme that has long been considered as a biomarker for melanoma as it catalyzes the oxidation of tyrosine and l-DOPA in melanogenesis. Recent studies also suggest a link between tyrosinase activity and Parkinson's disease; however, the mechanism of tyrosinase-mediated melanin formation in the brain is poorly understood. To better understand this connection, more advanced tools for the detection of tyrosinase in the brain are required. Herein, we successfully designed and synthesized a tyrosinase-targeting Gd(iii)-based MR contrast agent Tyr-GBCA 1. Tyr-GBCA 1 was synthesized by linking m-hydroxyphenyl to Gd-DOTA via a self-immolative linker. Tyr-GBCA 1 shows a 21% increase in the T1 relaxation rate (R1) in the presence of tyrosinase in artificial cerebral spinal fluid. Furthermore, Tyr-GBCA 1 is unreactive to hydrogen peroxide, which is a potential interferent in oxidation-based tyrosinase sensing systems. The reaction mechanism of the probe was studied by electrospray ionization (ESI) mass spectrometry and supports the cleavage of a reaction site.

| S-EPMC7028485 | biostudies-literature

Gadolinium Doping Enhances the Photoacoustic Signal of Synthetic Melanin Nanoparticles: A Dual Modality Contrast Agent for Stem Cell Imaging.

Project description:In this paper, we show that gadolinium-loaded synthetic melanin nanoparticles (Gd(III)-SMNPs) exhibit up to a 40-fold enhanced photoacoustic signal intensity relative to synthetic melanin alone and higher than other metal-chelated SMNPs. This property makes these materials useful as dual labeling agents because Gd(III)-SMNPs also behave as magnetic resonance imaging (MRI) contrast agents. As a proof-of-concept, we used these nanoparticles to label human mesenchymal stem cells. Cellular uptake was confirmed with bright-field optical and transmission electron microscopy. The Gd(III)-SMNP-labeled stem cells continued to express the stem cell surface markers CD73, CD90, and CD105 and proliferate. The labeled stem cells were subsequently injected intramyocardially in mice, and the tissue was observed by photoacoustic and MR imaging. We found that the photoacoustic signal increased as the cell number increased (R 2 = 0.96), indicating that such an approach could be employed to discriminate between stem cell populations with a limit of detection of 2.3 × 104 cells in in vitro tests. This multimodal photoacoustic/MRI approach combines the excellent temporal resolution of photoacoustics with the anatomic resolution of MRI.

| S-EPMC8045669 | biostudies-literature

Comparing the signal enhancement of a gadolinium based and an iron-oxide based contrast agent in low-field MRI.

Project description:Recently, there has been a renewed interest in low-field MRI. Contrast agents (CA) in MRI have magnetic behavior dependent on magnetic field strength. Therefore, the optimal contrast agent for low-field MRI might be different from what is used at higher fields. Ultra-small superparamagnetic iron-oxides (USPIOs), commonly used as negative CA, might also be used for generating positive contrast in low-field MRI. The purpose of this study was to determine whether an USPIO or a gadolinium based contrast agent is more appropriate at low field strengths. Relaxivity values of ferumoxytol (USPIO) and gadoterate (gadolinium based) were used in this research to simulate normalized signal intensity (SI) curves within a concentration range of 0-15 mM. Simulations were experimentally validated on a 0.25T MRI scanner. Simulations and experiments were performed using spin echo (SE), spoiled gradient echo (SGE), and balanced steady-state free precession (bSSFP) sequences. Maximum achievable SIs were assessed for both CAs in a range of concentrations on all sequences. Simulations at 0.25T showed a peak in SIs at low concentrations ferumoxytol versus a wide top at higher concentrations for gadoterate in SE and SGE. Experiments agreed well with the simulations in SE and SGE, but less in the bSSFP sequence due to overestimated relaxivities in simulations. At low magnetic field strengths, ferumoxytol generates similar signal enhancement at lower concentrations than gadoterate.

| S-EPMC8370648 | biostudies-literature

A cationic gadolinium contrast agent for magnetic resonance imaging of cartilage.

Project description:A new cationic gadolinium contrast agent is reported for delayed gadolinium enhanced magnetic resonance imaging of cartilage (dGEMRIC). The agent partitions into the glycosaminoglycan rich matrix of articular cartilage, based on Donnan equilibrium theory, and its use enables imaging of the human cadaveric metacarpal phalangeal joint.

| S-EPMC4841792 | biostudies-literature

Ultrafast 3D spin-echo acquisition improves Gadolinium-enhanced MRI signal contrast enhancement.

Project description:Long scan times of 3D volumetric MR acquisitions usually necessitate ultrafast in vivo gradient-echo acquisitions, which are intrinsically susceptible to magnetic field inhomogeneities. This is especially problematic for contrast-enhanced (CE)-MRI applications, where non-negligible T2* effect of contrast agent deteriorates the positive signal contrast and limits the available range of MR acquisition parameters and injection doses. To overcome these shortcomings without degrading temporal resolution, ultrafast spin-echo acquisitions were implemented. Specifically, a multiplicative acceleration factor from multiple spin echoes (×32) and compressed sensing (CS) sampling (×8) allowed highly-accelerated 3D Multiple-Modulation-Multiple-Echo (MMME) acquisition. At the same time, the CE-MRI of kidney with Gd-DOTA showed significantly improved signal enhancement for CS-MMME acquisitions (×7) over that of corresponding FLASH acquisitions (×2). Increased positive contrast enhancement and highly accelerated acquisition of extended volume with reduced RF irradiations will be beneficial for oncological and nephrological applications, in which the accurate in vivo 3D quantification of contrast agent concentration is necessary with high temporal resolution.

| S-EPMC4034007 | biostudies-literature

Quantification of amide proton transfer effect pre- and post-gadolinium contrast agent administration.

Project description:PurposeTo compare quantification of the amide proton transfer (APT) effect pre- and post-gadolinium contrast agent (Gd) administration in order to establish to what extent Gd alters quantification of the APT effect.Materials and methodsFour patients with internal carotid stenosis were recruited. APT imaging was acquired pre- and post-contrast in two sessions (before and after surgery) to assess the extent of relaxation time, T1 , change on APT effect calculated using magnetization transfer ratio asymmetry analysis at offsets of ±3.5 ppm relative to water resonance. Statistical and modeling evaluations were performed on the pre- and post-contrast APT effect to study the sensitivity to contrast administration.ResultsBefore surgery, the post-contrast T1 was estimated to drop <10% of the pre-value for the majority of the patients. After surgery, higher post-contrast T1 reductions were observed in all the patients (maximum decrease was about 20% of the pre-value). Consistent differences between pre- and post-contrast were seen in the APT effect quantified using the asymmetry measure in most regions of the brain, with significant differences found in the white matter at the group level and in 25% of the individual patient results.ConclusionAPT imaging should be performed prior to Gd administration to avoid potential misinterpretation of the APT effect.

| S-EPMC5524170 | biostudies-literature

MRI contrast agent for targeting glioma: interleukin-13 labeled liposome encapsulating gadolinium-DTPA.

Project description:BackgroundDetection of glioma with MRI contrast agent is limited to cases in which the blood-brain barrier (BBB) is compromised as contrast agents cannot cross the BBB. Thus, an early-stage infiltrating tumor is not detectable. Interleukin-13 receptor alpha 2 (IL-13Rα2), which has been shown to be overexpressed in glioma, can be used as a target moiety. We hypothesized that liposomes conjugated with IL-13 and encapsulating MRI contrast agent are capable of passing through an intact BBB and producing MRI contrast with greater sensitivity.MethodsThe targeted MRI contrast agent was created by encapsulating Magnevist (Gd-DTPA) into liposomes conjugated with IL-13 and characterized by particle size distribution, cytotoxicity, and MRI relaxivity. MR image intensity was evaluated in the brain in normal mice post injection of Gd-DTPA and IL-13-liposome-Gd-DTPA one day apart. The specificity for glioma detection by IL-13-liposome-Gd-DTPA was demonstrated in an intracranial glioma mouse model and validated histologically.ResultsThe average size of IL-13-liposome-Gd-DTPA was 137 ± 43 nm with relaxivity of 4.0 ± 0.4 L/mmole-s at 7 Tesla. No significant cytotoxicity was observed with MTS assay and serum chemistry in mice. The MRI signal intensity was enhanced up to 15% post injection of IL-13-liposome-Gd-DTPA in normal brain tissue following a similar time course as that for the pituitary gland outside of the BBB. MRI enhanced by IL-13-liposome-Gd-DTPA detected small tumor masses in addition to those seen with Magnevist-enhanced MRI.ConclusionsIL-13-liposome-Gd-DTPA is able to pass through the uncompromised BBB and detect an early stage glioma that cannot be seen with conventional contrast-enhanced MRI.

| S-EPMC4827043 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data