Magnetic resonance fingerprinting based on realistic vasculature in mice.

Magnetic resonance fingerprinting (MRF) was recently proposed as a novel strategy for MR data acquisition and analysis. A variant of MRF called vascular MRF (vMRF) followed, that extracted maps of three parameters of physiological importance: cerebral oxygen saturation (SatO2), mean vessel radius and cerebral blood volume (CBV). However, this estimation was based on idealized 2-dimensional simulations of vascular networks using random cylinders and the empirical Bloch equations convolved with a diffusion kernel. Here we focus on studying the vascular MR fingerprint using real mouse angiograms and physiological values as the substrate for the MR simulations. The MR signal is calculated ab initio with a Monte Carlo approximation, by tracking the accumulated phase from a large number of protons diffusing within the angiogram. We first study the identifiability of parameters in simulations, showing that parameters are fully estimable at realistically high signal-to-noise ratios (SNR) when the same angiogram is used for dictionary generation and parameter estimation, but that large biases in the estimates persist when the angiograms are different. Despite these biases, simulations show that differences in parameters remain estimable. We then applied this methodology to data acquired using the GESFIDE sequence with SPIONs injected into 9 young wild type and 9 old atherosclerotic mice. Both the pre injection signal and the ratio of post-to-pre injection signals were modeled, using 5-dimensional dictionaries. The vMRF methodology extracted significant differences in SatO2, mean vessel radius and CBV between the two groups, consistent across brain regions and dictionaries. Further validation work is essential before vMRF can gain wider application.

Superparamagnetic iron oxide based nanoprobes for imaging and theranostics.

The need to target, deliver and subsequently evaluate the efficacy of therapeutics in the treatment of a disease has provided added impetus in developing novel and highly efficient contrast agents. Superparamagnetic iron oxide nanoparticles (SPIONs) have offered tremendous potential in designing advanced magnetic resonance imaging (MRI) diagnostic agents, due to their unique physicochemical properties. There has been tremendous effort devoted in the recent past in developing synthetic methodologies through which their size, hydrodynamic radii, chemical composition and morphologies could be tailored at the nanoscale. This enables one to fine tune their magnetic behavior, and thus their MRI response. While novel synthetic strategies are being assembled for directing SPIONs to the diseased site as well as imparting them stealth and biocompatibility, it is also essential to evaluate their biological toxicological profiles. This review highlights recent advances that have been made in the synthesis of SPIONs, subsequent functionalization with desired entities, and a discussion on their use as MRI contrast agents in cardiovascular research.

VCAM-1-targeting gold nanoshell probe for photoacoustic imaging of atherosclerotic plaque in mice.

The development of molecular probes and novel imaging modalities, allowing better resolution and specificity, is associated with an increased potential for molecular imaging of atherosclerotic plaques especially in basic and pre-clinical research applications. In that context, a photoacoustic molecular probe based on gold nanoshells targeting VCAM-1 in mice (immunonanoshells) was designed. The molecular probe was validated in vitro and in vivo, showing no noticeable acute toxic effects. We performed the conjugation of gold nanoshells displaying near-infrared absorption properties with VCAM-1 antibody molecules and PEG to increase their biocompatibility. The resulting immunonanoshells obtained under different conditions of conjugation were then assessed for specificity and sensitivity. Photoacoustic tomography was performed to determine the ability to distinguish gold nanoshells from blood both in phantoms and in vivo. Ex vivo optical projection tomography of hearts and aortas from atherosclerotic and control mice confirmed the selective accumulation of the immunonanoshells in atherosclerotic-prone regions in mice, thus validating the utility of the probe in vivo in small animals for pre-clinical research. These immunonanoshells represent an adequate mean to target atherosclerotic plaques in small animals, leading to new tools to follow the effect of therapies on the progression or regression of the disease.

Tailoring the efficacy of nimodipine drug delivery using nanocarriers based on A2B miktoarm star polymers.

We report a nanocarrier based on A(2)B type miktoarm polymers (A=polyethylene glycol (PEG); B=polycaprolactone (PCL)) for nimodipine (NIM), a hydrophobic drug with very poor aqueous solubility that is commonly prescribed for the prevention and treatment of delayed ischemic neurological disorders. The A(2)B star polymers were constructed on a core with orthogonal functionalities that facilitated the performance of "click" chemistry followed by ring-opening polymerization. These star polymers assemble into spherical micelles into which NIM can be easily loaded by the co-solvent evaporation method. The micelles obtained from the star polymer PEG775(2)-PCL5800 showed NIM encapsulation efficiency of up to 78 wt% at a feed weight ratio of 5.0%. The loading efficiency of the micelles was dependent on the length of the PCL arm in the A(2)B miktoarm polymers. Aqueous solubility of NIM was increased by approximately 200 fold via micellar encapsulation. The in vitro release of NIM from the micelles was found to occur at a much slower rate than from its solution. Lipopolysaccharide induced nitric oxide production in N9 microglia cells was reduced in the presence of micelle-encapsulated NIM, as well as in the presence of micelles alone. The treatment of microglia with micelle-encapsulated NIM reduced the release of TNF-alpha, a pro-inflammatory cytokine. These results suggest that NIM-loaded miktoarm micelles could be useful in the treatment of neuroinflammation.

Dendrimer templated construction of silver nanoparticles.

Silver nanoparticles continue to evoke great current interest due to their tremendous potential in designing smart materials for a wide variety of applications. Much emphasis has been placed lately in developing methodologies that could modulate the size and shape of these metal particles. Dendrimers that are monodisperse in nature with a regular and highly branched three-dimensional architecture, provide a useful platform to accomplish this goal. These hyperbranched macromolecules have been widely explored as templates in the construction of silver metal nanoparticles, and this review aims to provide a detailed overview of dendrimer-assisted synthesis of silver nanoparticles.

"Click" methodologies: efficient, simple and greener routes to design dendrimers.

Designing dendrimers that are monodisperse hyperbranched macromolecules and offer significant potential in numerous scientific fields, is becoming a major topical area in modern research. Among the challenges of the 21st century, synthetic methodologies that increase efficiency of conversion and a greener chemistry approach, are expected to lead the way in the quest to build novel nanomaterials. The recent entry of so-called "click" reactions that include Diels-Alder, Cu(I)-catalyzed Huisgen cycloaddition and thiol-ene coupling, have generated real stimulus not only in developing elegant materials of choice, but also in making the leap to industrial scale build-up of dendritic macromolecules. This tutorial review takes on the task of demonstrating the simplicity of these "click" reactions and the advantages they offer from a synthetic view point in developing mono- to multifunctional dendrimers. A brief introduction to "click" chemistry is followed by a chronological survey of developments in the field, and the impact these have had in designing novel dendritic macromolecules. The review is intended to introduce scientists to these highly efficient methodologies with demonstrated potential, and provide impetus for further growth of the area.

Diels-Alder "click" chemistry in designing dendritic macromolecules.

In the current decade, design of dendritic macromolecules including dendrimers and polymers has reached a new era, mainly due to the remarkably successful and elegant synthetic routes that have been developed recently. This survey aims at demonstrating the potential of the Diels-Alder "click" chemistry, a very effective, simple and versatile synthetic tool in the formation of complex and functional nanometer-sized assemblies. The role of retro Diels-Alder reaction is also explored to highlight the increasing competitive potential of this strategy in the design of dendritic macromolecules of topical interest. The potential "green" nature of this methodology in constructing macromolecular assemblies is also evaluated.

Self-assembled monolayers: solidification of carbamazepine in Form II at an interface.

A self-assembled monolayer incorporating well-spaced biphenyl moieties initiates solidification of carbamazepine at its interface. A detailed analysis of the resulting crystals using X-ray powder diffraction, FTIR-ATR as well as thermomicroscopy, indicates a preference for its crystallization in trigonal (Form II) polymorph.

Templated crystallization of octadecanol on patterned nanoassemblies.

A serial templating methodology using linked aminosilane/stannane units and simple beaker chemistry yields thin film nanoassemblies on semiconductor surfaces that provide nucleating sites for crystallization of octadecanol, the morphologies of which could be tailored using subtle variations in the backbone structure of bridged aminosilane/stannanes.