Nanostructured T1 MRI contrast agents

Recent advances on new T1 MRI contrast agents using nanostructured materials will be presented. Paramagnetic Gd(3+) ions have been immobilized in nanostructured matrices such as liposomes, perfluorocarbons, silica-based nanoparticles, emulsions, and carbon nanotube to generate nanostructured ionic T1 MRI contrast agents with high relaxivity. Inorganic nanoparticles of gadolinium compounds and manganese oxides have been recently developed as new types of T1 MRI contrast agents using the large surface concentration of metal ions with high magnetic moments. Functionalization of these nanostructured T1 contrast agents enabled targeted imaging, multimodal imaging, and simultaneous imaging and drug delivery.

Inorganic nanoparticles for MRI contrast agents

Various inorganic nanoparticles have been used as magnetic resonance imaging (MRI) contrast agents due to their unique properties, such as large surface area and efficient contrasting effect. Since the first use of super-paramagnetic iron oxide (SPIO) as a liver contrast agent, nanoparticulate MRI contrast agents have attracted a lot of attention. Magnetic iron oxide nanoparticles have been extensively used as MRI contrast agents due to their ability to shorten T2* relaxation times in the liver, spleen, and bone marrow. More recently, uniform ferrite nanoparticles with high crystallinity have been successfully employed as new T2 MRI contrast agents with improved relaxation properties. Iron oxide nanoparticles functionlized with targeting agents have been used for targeted imaging via the site-specific accumulation of nanoparticles at the targets of interest. Recently, extensive research has been conducted to develop nanoparticle-based T1 contrast agents to over-come the drawbacks of iron oxide nanoparticle-based negative T2 contrast agents. In this report, we summarize the recent progress in inorganic nanoparticle-based MRI contrast agents.

Synthesis of nanorattles composed of gold nanoparticles encapsulated in mesoporous carbon and polymer shells

In this study, we fabricated new spherical silica templates with submicrometer sized solid cores containing an encapsulated Au nanoparticle surrounded by a mesoporous shell structure. Hollow spherical carbon and polymer capsules, containing gold nanoparticles, were synthesized using these silica templates. The resulting carbon capsules inversely replicated the structure of the silica template and contained uniform pores with a narrow pore size distribution centered at 3.8 nm. These carbon capsules exhibited a BET surface area of >1000 m(2) g(-1) and a total pore volume of >1.0 cm(3) g(-1). In addition, hollow polymer capsules having a well-defined pore size were fabricated using a similar synthetic procedure.

Design Of A Multi-Dopamine-Modified Polymer Ligand Optimally Suited For Interfacing Magnetic Nanoparticles With Biological Systems

We have designed a set of multifunctional and multicoordinating polymer ligands that are optimally suited for surface functionalizing iron oxide and potentially other magnetic nanoparticles (NPs) and promoting their integration into biological systems. The amphiphilic polymers are prepared by coupling (via nucleophilic addition) several amine-terminated dopamine anchoring groups, poly(ethylene glycol) moieties, and reactive groups onto a poly(isobutylene-alt- maleic anhydride) (PIMA) chain. This design greatly benefits from the highly efficient and reagent-free one-step reaction of maleic anhydride groups with amine-containing molecules. The availability of several dopamine groups in the same ligand greatly enhances the ligand affinity, via multiple coordination, to the magnetic NPs, while the hydrophilic and reactive groups promote colloidal stability in buffer media and allow subsequent conjugation with target biomolecules. Iron oxide nanoparticles ligand exchanged with these polymer ligands have a compact hydrodynamic size and exhibit enhanced long-term colloidal stability over the pH range of 4-12 and in the presence of excess electrolytes. Nanoparticles ligated with terminally reactive polymers have been easily coupled to target dyes and tested in live cell imaging with no measurable cytotoxicity. Finally, the resulting hydrophilic nanoparticles exhibit large and size-dependent r2 relaxivity values. © 2014 American Chemical Society

Paramagnetic inorganic nanoparticles as T1 MRI contrast agents

Magnetic resonance imaging (MRI) is one of the most powerful molecular imaging techniques and can noninvasively visualize and quantify biological processes within the living organisms. The introduction of exogenous contrast agents has allowed specific visualization of biological targets as well as enhanced the sensitivity of MRI. Recently, paramagnetic inorganic nanoparticles showing positive T-1 contrast effect have been investigated as T-1 MRI contrast agents. Since the first trials of spherical nanoparticles of manganese oxide and gadolinium oxide, inorganic nanoparticles of various compositions and shapes have been used for in vivo and in vitro MRI because of their distinct signal enhancement in MR images. However, for clinical applications, important and complex issues such as safety and efficiency should be investigated by active research encompassing multiple disciplines, including chemistry, biology, biomedical engineering, and medicine. (C) 2013 Wiley Periodicals, Inc.

Poly(ethylene glycol)-Based Multidentate Oligomers for Biocompatible Semiconductor and Gold Nanocrystals

We have developed a new set of multifunctional multidentate OligoPEG ligands, each containing a central oligomer on which were laterally grafted several short poly­(ethylene glycol) (PEG) moieties appended with either thioctic acid (TA) or terminally reactive groups. Reduction of the TAs (e.g., in the presence of NaBH₄) provides dihydrolipoic acid (DHLA)-appended oligomers. Here the insertion of PEG segments in the ligand structure promotes water solubility and reduces nonspecific interactions, while TA and DHLA groups provide multidentate anchoring onto Au nanoparticles (AuNPs) and ZnS-overcoated semiconductor quantum dots (QDs), respectively. The synthetic route involves simple coupling chemistry using <i>N</i>,<i>N</i>-dicylohexylcarbodiimide (DCC). Water-soluble QDs and AuNPs capped with these ligands were prepared via cap exchange. As prepared, the nanocrystals dispersions were aggregation-free, homogeneous, and stable for extended periods of time over pH ranging from 2 to 14 and in the presence of excess electrolyte (2 M NaCl). The new OligoPEG ligands also allow easy integration of tunable functional and reactive groups within their structures (e.g., azide or amine), which imparts surface functionalities to the nanocrystals and opens up the possibility of bioconjugation with specific biological molecules. The improved colloidal stability combined with reactivity offer the possibility of using the nanocrystals as biological probes in an array of complex and biologically relevant media

Anti-Galvanic Reduction of Silver Ion on Gold and Its Role in Anisotropic Growth of Gold Nanomaterials

The role of silver ions in the seed-mediated growth of gold nanostructures has been investigated. Silver submonolayer or monolayer on specific facet of gold is assumed in previously suggested mechanism owing to underpotential deposition (UPD) of silver by ascorbic acid having weak reducing power. Silver overpotential deposition by ascorbic acid, however, is confirmed by electrochemical stripping voltammetry, whereas submonolayer of silver on gold is spontaneously formed by anti-galvanic reduction in the absence of ascorbic acid. In the presence of cetyl­trimethyl­ammonium bromide (CTAB), silver overpotential deposition by ascorbic acid does not occur, but submonolayer of silver is formed on gold surface. Adsorption of silver and CTAB on gold dramatically hindered the electron transfer by the oxidation of ascorbic acid on gold, which reduces gold ions to metallic gold in seed-mediated growth. These results provide the evidence to the in-depth observation of mechanism in seed-mediated growth where the blocking effect of CTAB/Ag­(submonolayer)/Au for oxidation of reducing agent determine the shape and facet of gold nanomaterials

In vitro cytotoxicity screening of water-dispersible metal oxide nanoparticles in human cell lines

In this study, we present in vitro cytotoxicity of iron oxide (Fe 3O4) and manganese oxide (MnO) using live/dead cell assay, lactate dehydrogenase assay, and reactive oxygen species detection with variation of the concentration of nanoparticles (5-500 ??g/ml), incubation time (18-96 h), and different human cell lines (lung adenocarcinoma, breast cancer cells, and glioblastoma cells). The surface of nanoparticles is modified with polyethyleneglycol-derivatized phospholipid to enhance the biocompatibility, water-solubility, and stability under an aqueous media. While the cytotoxic effect was negligible for 18 h incubation even at highest concentration of 500 ??g/ml, MnO nanoparticle represented higher level of toxicity than those of Fe3O4 and the commercial medical contrast reagent, Feridex after 2 and 4 day incubation time. However, the cytotoxicity of Fe3O4 is equivalent or better than Feridex based on the live/dead cell viability assay. The engineered MnO and Fe 3O4 exhibited excellent stability compared with Feridex for a prolonged incubation time. &#169; 2009 Springer-Verlag.close383