Water-dispersible superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by thermal decomposition of iron(III) acetylacetonate in the presence of triethylene glycol (TREG). The resulting TREG-coated SPIONs were not stable, undergoing agglomeration and loss of the TREG coating under prolonged storage at 37 °C or in the presence of increased saline concentrations. To avoid these problems, stable colloidal TREG-coated SPIONs were obtained by two different procedures: (i) dimercaptosuccinic acid (DMSA) ligand-exchange reactions to obtain DMSA-coated SPIONs and (ii) chemical modification of the TREG coating. Both procedures, but especially the DMSA exchange, increased the stability of the SPION suspension. Finally, the functionality of both types of particles for biological applications was demonstrated by conjugating a model antibody to the end carboxyl groups of the SPIONs and testing the immunoreactivity of the final antibody–particle conjugates by an enzyme-linked immunosorbent assay (ELISA).

The nucleation and growth of water dispersible iron-oxide nanoparticles synthesized by high temperature decomposition of iron(III) acetylacetonate in the presence of different solvents has been studied. A battery of techniques was used to characterize the products obtained under different conditions and to elucidate the synthesis mechanism. Results show that the synthesis of iron-oxide nanoparticles in triethylene glycol (TEG) proceeds through a multistep process whose first stage is likely to be the formation of an intermediate TEG-iron-complex that evolves into a low-crystallinity iron-oxide-organic precursor during aging at 180 °C. Raising the temperature above 240 °C caused the thermal decomposition of the precursor and the sudden nucleation of small iron-oxide nanocrystals. Keeping the reactant mixture at 280 °C led to the growth of iron-oxide nanocrystals, as did increasing the time at reflux temperature, the amount of initial iron precursor or the use high boiling point solvents. The particle size could be reproducibly controlled between 1.5 and 13 nm, with a relatively narrow size distribution. Larger particles could also be obtained using a solvothermal method in an autoclave reactor.

We report here a detailed structural and magnetic study of different silica nanocapsules containing uniform and highly crystalline maghemite nanoparticles. The magnetic phase consists of 5 nm triethylene glycol (TREG)- or dimercaptosuccinic acid (DMSA)-coated maghemite particles. TREG-coated nanoparticles were synthesized by thermal decomposition. In a second step, TREG ligands were exchanged by DMSA. After the ligand exchange, the ζ potential of the particles changed from -10 to -40 mV, whereas the hydrodynamic size remained constant at around 15 nm. Particles coated by TREG and DMSA were encapsulated in silica following a sol-gel procedure. The encapsulation of TREG-coated nanoparticles led to large magnetic aggregates, which were embedded in coalesced silica structures. However, DMSA-coated nanoparticles led to small magnetic clusters inserted in silica spheres of around 100 nm. The final nanostructures can be described as the result of several competing factors at play. Magnetic measurements indicate that in the TREG-coated nanoparticles the interparticle magnetic interaction scenario has not dramatically changed after the silica encapsulation, whereas in the DMSA-coated nanoparticles, the magnetic interactions were screened due to the function of the silica template. Moreover, the analysis of the AC susceptibility suggests that our systems essentially behave as cluster spin glass systems.

BackgroundMagnetic resonance imaging (MRI) plays an important role in tumor detection/diagnosis. The use of exogenous contrast agents (CAs) helps to improve the discrimination between lesion and neighbouring tissue, but most of the currently available CAs are non-specific. Assessing the performance of new, selective CAs requires exhaustive assays and large amounts of material. Accordingly, in a preliminary screening of new CAs, it is important to choose candidate compounds with good potential for in vivo efficiency. This screening method should reproduce as close as possible the in vivo environment. In this sense, a fast and reliable method to select the best candidate CAs for in vivo studies would minimize time and investment cost, and would benefit the development of better CAs.ResultsThe post-mortem ex vivo relative contrast enhancement (RCE) was evaluated as a method to screen different types of CAs, including paramagnetic and superparamagnetic agents. In detail, sugar/gadolinium-loaded gold nanoparticles (Gd-GNPs) and iron nanoparticles (SPIONs) were tested. Our results indicate that the post-mortem ex vivo RCE of evaluated CAs, did not correlate well with their respective in vitro relaxivities. The results obtained with different Gd-GNPs suggest that the linker length of the sugar conjugate could modulate the interactions with cellular receptors and therefore the relaxivity value. A paramagnetic CA (GNP (E_2)), which performed best among a series of Gd-GNPs, was evaluated both ex vivo and in vivo. The ex vivo RCE was slightly worst than gadoterate meglumine (201.9 ± 9.3% versus 237 ± 14%, respectively), while the in vivo RCE, measured at the time-to-maximum enhancement for both compounds, pointed to GNP E_2 being a better CA in vivo than gadoterate meglumine. This is suggested to be related to the nanoparticule characteristics of the evaluated GNP.ConclusionWe have developed a simple, cost-effective relatively high-throughput method for selecting CAs for in vivo experiments. This method requires approximately 800 times less quantity of material than the amount used for in vivo administrations.