Multimodal Imaging Contrast Agents Research Articles

Magnetic Alloy Nanorings Loaded with Gold Nanoparticles: Synthesis and Applications as Multimodal Imaging Contrast Agents

AbstractMulticomponent Ni7Co3 alloy–Au nanorings can be facilely synthesized at room temperature using metallic Ni7Co3 alloy nanorings as both reducing agent and sacrificial template in water. These novel alloy–Au hybrid nanorings are well biocompatible due to coating with poly(vinylpyrrolidone) and gold nanoparticles. When increasing the molar ratio of alloy to gold salt from 1:1 to 5:1, the number of the gold nanoparticles loaded on the surface of alloy nanorings were found to be decreased, and their morphology was transformed from rod to particle, remaining the ring‐like assemblies. Their saturation magnetization increased due to the ring‐like assemblies, resulting in the enhancement of the signal intensity in Spin–spin relaxation time (T2) weighted magnetic resonance imaging measurement. These alloy–Au hybrid nanocomposites can perform as multimodal imaging contrast agents for cancer cell diagnosis by two‐photon fluorescent imaging and T2‐weighted magnetic resonance imaging. In addition, their potential application for photothermal therapy was preliminarily investigated.

In Vitro and in Vivo Studies of FePt Nanoparticles for Dual Modal CT/MRI Molecular Imaging

The water-solvable FePt nanoparticles of 3, 6, and 12 nm in diameter (3 nm-, 6 nm-, and 12 nm-FePt) were synthesized and applied as a dual modality contrast agent for CT/MRI molecular imaging. These nanoparticles present excellent biocompatibility and hemocompatibility in all test concentrations for the imaging contrast. The biodistribution analysis revealed the highest serum concentration and circulation half-life for 12 nm-FePt, followed by 6 nm-FePt then 3 nm-FePt. Thus, the 3 nm-FePt showed higher brain concentrations. Anti-Her2 antibody conjugated FePt nanoparticles demonstrated molecular expression dependent CT/MRI dual imaging contrast effect in MBT2 cell line and its Her2/neu gene knock out counterpart. Selective contrast enhancement of Her2/neu overexpression cancer lesions in both CT and MRI was found in tumor bearing animal after tail vein injection of the nanoparticles. The 12 nm-FePt outperformed 3 nm-FePt in both imaging modalities. These results indicate the potential of FePt nanoparticles to serve as novel multimodal molecular imaging contrast agents in clinical settings.

Perfluorodecalin/[InGaP/ZnS quantum dots] nanoemulsions as 19F MR/optical imaging nanoprobes for the labeling of phagocytic and nonphagocytic immune cells

Multimodal imaging contrast agents with unique magnetic resonance (MR) and optical imaging capabilities have great potentials in the diagnosis and therapy of disease. Using a rational materials design approach, the bimodal imaging contrast agent, perfluorodecalin (PFD)/[InGaP/ZnS quantum dots (QDs)] composite nanoemulsions is developed in this study. 19F molecules in the PFD/[InGaP/ZnS QDs] nanoemulsions provide a 19F-based MR imaging capability, while fluorescent QDs dispersed in PFD nanodroplets provide an optical imaging modality. This study also demonstrates that these bimodal imaging contrast agents can be delivered easily into both phagocytic and nonphagocytic immune cells. Internalization of multifunctional PFD/[InGaP/ZnS QDs] nanoemulsions into immunotherapeutic cells permits the labeled cells to be imaged by both magnetic resonance and fluorescence imaging with little effect on cell viability and function. The results of our study highlight the potential of PFD/[InGaP/ZnS QDs] nanoemulsion as a bimodal imaging nanoprobe for molecular imaging in immune cell-based cancer therapies.

Carbon nanotube-based magnetic-fluorescent nanohybrids as highly efficient contrast agents for multimodal cellular imaging

We developed a simple and novel layer-by-layer (LBL) assembly in combination with covalent connection strategy for the synthesis of multifunctional carbon nanotubes (CNTs)-based magnetic-fluorescent nanohybrids as multimodal cellular imaging agents for detecting human embryonic kidney (HEK) 293T cells via magnetic resonance (MRI) and confocal fluorescence imaging. Superparamagnetic iron oxide nanoparticles (SPIO) and near-infrared fluorescent CdTe quantum dots (QDs) were covalently coupled on the surface of CNTs in sequence via LBL assembly. It was indicated that the SPIO layer acted not only as a contrast agent for MRI, but also as a spacer between CdTe QDs and CNTs for prohibiting fluorescence quenching of QDs on the surface of the CNTs. The multifunctional CNT-based magnetic-fluorescent nanohybrids showed an enhanced MRI signal as contrast agent for detecting 293T cells in comparison with the pure SPIO. This is due to the magnetic coupling between the orderly arrayed SPIO, the function of CNTs for lowering the transverse relaxation and the ability of CNTs for penetrating into cells. Moreover, the multifunctional CNT-based magnetic-fluorescent nanohybrids exhibited the higher intracellular labeling efficiency due to the ability of CNTs for penetrating into cells in comparison with pure SPIO-CdTe nanoparticles.

High-Density Lipoprotein–Based Contrast Agents for Multimodal Imaging of Atherosclerosis

Lipoproteins, natural nanoparticles, have a well-recognized biological role and are highly suitable as a platform for delivering imaging agents. The ease with which both the exterior and interior of the particles can be modified permits the creation of multifunctional nanoparticles for imaging as well as the delivery of therapeutics. Importantly, their endogenous nature may make them biocompatible and biodegradable and allows them to avoid the recognition of the reticuloendothelial system. In particular, high-density lipoproteins (HDL) are of interest, because of their small size they can easily cross the endothelium and penetrate the underlying tissue. We summarize here the progress in establishing HDL as a vector for delivering a variety of diagnostically active materials to vulnerable atherosclerotic plaques in mouse models of atherosclerosis. By loading various types of image-enhancing compounds into either the core or surface of HDL, they can be visualized by different imaging modalities (MRI, CT, optical). By rerouting of HDL away from plaque macrophages, imaging of biological processes in diseases besides atherosclerosis may also be achieved.

Gold Nanorods Coated with Multilayer Polyelectrolyte as Contrast Agents for Multimodal Imaging

Gold nanorods coated with multilayer polyelectrolyte is reported as a biocompatible optical probe with capability for dark-field imaging and for electron microscopy of cancer cells. Transferrin (Tf) was conjugated to the polyelectrolyte-coated nanorods for targeted in vitro delivery to cancer cells. Dark-field imaging was used to confirm the receptor-mediated uptake of nanorods into HeLa cells, which is known to overexpress the transferrin receptor (TfR). Minimal uptake was observed with untargeted nanorods. Electron microscopy was used to confirm that the intracellular uptake of the nanorods predominantly occurred via the Tf−TfR interaction and the nanorods localized in vesicular structures such as endosomes.

Molecular imaging of VEGF receptors in angiogenic vasculature with single-chain VEGF-based probes

We describe a new generation of protein-targeted contrast agents for multimodal imaging of the cell-surface receptors for vascular endothelial growth factor (VEGF). These receptors have a key role in angiogenesis and are important targets for drug development. Our probes are based on a single-chain recombinant VEGF expressed with a cysteine-containing tag that allows site-specific labeling with contrast agents for near-infrared fluorescence imaging, single-photon emission computed tomography or positron emission tomography. These probes retain VEGF activities in vitro and undergo selective and highly specific focal uptake into the vasculature of tumors and surrounding host tissue in vivo. The fluorescence contrast agent shows long-term persistence and co-localizes with endothelial cell markers, indicating that internalization is mediated by the receptors. We expect that multimodal imaging of VEGF receptors with these probes will be useful for clinical diagnosis and therapeutic monitoring, and will help to accelerate the development of new angiogenesis-directed drugs and treatments.

Nanoscale Metal−Organic Frameworks as Potential Multimodal Contrast Enhancing Agents

Nanoscale metal-organic frameworks (NMOFs) based on Gd3+ centers and benzenedicarboxylate and benzenetricarboxylate bridging ligands were synthesized using reverse microemulsions and characterized using SEM, PXRD, and TGA. These NMOFs exhibit extraordinarily large R1 and R2 relaxivities because of the presence of up to tens of millions of Gd3+ centers in each nanoparticle and are thus efficient T1 and T2 contrast agents for MRI. The NMOFs can also be made highly luminescent by doping with Eu3+ or Tb3+ centers. The results from this work suggest that NMOFs can be used as potential contrast agents for multimodal imaging.