Quantitative assessment of binding affinities for nanoparticles targeted to vulnerable plaque.

Recent successes in targeted immune and cell-based therapies have driven new directions for pharmaceutical research. With the rise of these new therapies there is an unfilled need for companion diagnostics to assess patients' potential for therapeutic response. Targeted nanomaterials have been widely investigated to fill this niche; however, in contrast to small molecule or peptide-based targeted agents, binding affinities are not reported for nanomaterials, and to date there has been no standard, quantitative measure for the interaction of targeted nanoparticle agents with their targets.

Multimodality PET/MRI agents targeted to activated macrophages.

The recent emergence of multimodality imaging, particularly the combination of PET and MRI, has led to excitement over the prospect of improving detection of disease. Iron oxide nanoparticles have become a popular platform for the fabrication of PET/MRI probes owing to their advantages of high MRI detection sensitivity, biocompatibility, and biodegradability. In this article, we report the synthesis of dextran-coated iron oxide nanoparticles (DIO) labeled with the positron emitter (64)Cu to generate a PET/MRI probe, and modified with maleic anhydride to increase the negative surface charge.

Size-stable solid lipid nanoparticles loaded with Gd-DOTA for magnetic resonance imaging.

Solid lipid nanoparticles (SLNs) have recently emerged as nontoxic, versatile alternatives to traditional carriers (liposomes, polymeric nanoparticles) for drug delivery. Because SLNs are composed of a solid lipid core, they offer significant protection against chemical degradation of their drug cargo and offer the potential for controlled release. SLNs also hold promise for use as targeted agents and multimodal imaging agents.

Strategies for the development of gadolinium-based 'q'-activatable MRI contrast agents.

The emergence and rapid development of activatable contrast agents (CAs), whose relaxivity changes in response to the variation of a specific marker in the surrounding physiological microenvironment, have expanded the scope of MRI beyond anatomical and functional imaging to also convey information at the cellular and molecular level. The essence of an activatable MRI CA is the difference in relaxivity before and after a change in a physiological variable: the larger the difference, the better the CA. In this review, strategies for the design of activatable gadolinium CAs, with a switching mechanism based on the modulation of hydration (q), sensitive to common variables in the physiological microenvironment, such as pH, light, redox and metal ions, are illustrated and discussed.

Reversible low-light induced photoswitching of crowned spiropyran-DO3A complexed with gadolinium(III) ions.

Photoswitchable spiropyran has been conjugated to the crowned ring system DO3A, which improves its solubility in dipolar and polar media and stabilizes the merocyanine isomer. Adding the lanthanide ion gadolinium(III) to the macrocyclic ring system leads to a photoresponsive magnetic resonance imaging contrast agent that displays an increased spin-lattice relaxation time (T₁) upon visible light stimulation. In this work, the photoresponse of this photochromic molecule to weak light illumination using blue and green light emitting diodes was investigated, simulating the emission spectra from bioluminescent enzymes.

Development of iron-doped silicon nanoparticles as bimodal imaging agents.

We demonstrate the synthesis of water-soluble allylamine-terminated Fe-doped Si (Si(xFe)) nanoparticles as bimodal agents for optical and magnetic imaging. The preparation involves the synthesis of a single-source iron-containing precursor, Na(4)Si(4) with x% Fe (x = 1, 5, 10), and its subsequent reaction with NH(4)Br to produce hydrogen-terminated Si(xFe) nanoparticles. The hydrogen-capped nanoparticles are further terminated with allylamine via thermal hydrosilylation.

Nanoformulations for molecular MRI.

Nanoscale contrast agents have shown the ability to increase the detection sensitivity of magnetic resonance imaging (MRI) by several orders of magnitude, endowing this traditionally macroscopic modality with the ability to observe unique molecular signatures. Herein, we describe three types of nanoparticulate contrast agents: iron oxide nanoparticles, gadolinium-based nanoparticles, and bio-essential manganese, cobalt, nickel, and copper ion-containing nanoformulations. Some of these agents have been approved for clinical use, but more are still under development for medical imaging.

Receptor-targeted iron oxide nanoparticles for molecular MR imaging of inflamed atherosclerotic plaques.

In a number of literature reports iron oxide nanoparticles have been investigated for use in imaging atherosclerotic plaques and found to accumulate in plaques via uptake by macrophages, which are critical in the process of atheroma initiation, propagation, and rupture. However, the uptake of these agents is non-specific; thus the labeling efficiency for plaques in vivo is not ideal. We have developed targeted agents to improve the efficiency for labeling macrophage-laden plaques.

PET Imaging and Biodistribution of Silicon Quantum Dots in Mice.

Investigation of nanomaterial disposition and fate in the body is critical before such material can be translated into clinical application. Herein a new macrocyclic ligand-(64)Cu(2+) complex was synthesized and used to label dextran-coated silicon quantum dots (QD), with an average hydrodynamic diameter of 15.1 ± 7.

Activatable T₁ and T₂ magnetic resonance imaging contrast agents.

Magnetic resonance imaging (MRI) has become one of the most important diagnosis tools available in medicine. Typically MRI is not capable of sensing biochemical activities. However, recently emerged activatable MRI contrast agents (CAs), whose relaxivity is variable in response to a specific parameter change in the surrounding physiological microenvironment, potentially allow for MRI to indicate biological processes.

Modulation of T2 relaxation time by light-induced, reversible aggregation of magnetic nanoparticles.

A reversible T2 contrast agent consisting of cross-linked anionic dextran coated iron oxide nanoparticles covalently coupled to a light-sensitive spiropyran (SP)/merocyanine (MC) motif was synthesized and characterized. In aqueous solution, light induced isomerization of the molecular switches between the hydrophobic SP isomer and hydrophilic MC isomer directs the aggregation and dispersion of the nanoparticles, respectively. When in the dark, where the MC form dominates, the probe has a T2 relaxation time of 37.

Synthesis and characterization of a redox- and light-sensitive MRI contrast agent.

A redox- and light-sensitive, T(1)-weighted magnetic resonance imaging (MRI) contrast agent which tethers a spiropyran(SP)/merocyanine(MC) motif to a Gd-DO3A moiety was synthesized and characterized. When in the dark, the probe is in its MC form which has an r(1) relaxivity of 2.51 mM(-1)s(-1) (60MHz, 37°C).

Paramagnetic, silicon quantum dots for magnetic resonance and two-photon imaging of macrophages.

Quantum dots (QDs) are an attractive platform for building multimodality imaging probes, but the toxicity for typical cadmium QDs limits enthusiasm for their clinical use. Nontoxic, silicon QDs are more promising but tend to require short-wavelength excitations which are subject to tissue scattering and autofluorescence artifacts. Herein, we report the synthesis of paramagnetic, manganese-doped, silicon QDs (Si(Mn) QDs) and demonstrate that they are detectable by both MRI and near-infrared excited, two-photon imaging.

Photochromically-controlled, reversibly-activated MRI and optical contrast agent.

The contrast agent which tethers a spiropyran group to a Gd-DO3A moiety has higher relaxivity and fluorescence intensity in the dark; the relaxivity and fluorescence intensity decrease after irradiation with visible light.

Di-ionizable p-tert-butylcalix[4]arene-1,2-crown-5 and -crown-6 compounds in the cone conformation: synthesis and alkaline earth metal cation extraction.

Di-ionizable p-tert-butylcalix[4]arene-1,2-crown-5 and -crown-6 ethers in the cone conformation were prepared and their conformations and regioselectivities were verified by NMR spectroscopy. The metal ion-complexing properties of these ligands were evaluated by competitive solvent extractions of alkaline earth metal cations from water into chloroform. The ligands were found to be efficient extractants with selectivity for Ba(2+).