Magnetic iron oxide nanoparticles (MNPs) have been prepared and stabilized with three organic acids (tartaric, malic and ascorbic) in order to obtain biocompatible and water dispersible MNPs with potential to bind specifically to tumoral cancer cells. An in deep characterization was performed aiming to verify the presence and effect of the coating and stabilizer on MNPs surface. Besides the mechanisms followed by the different acids to bind MNPs were elucidated and used to justify the differences in the physicochemical properties of each formulation. Data related to characterization revealed that MNPs coated with ascorbic acid (MNPs-AA) resulted the most suitable in terms of their size, surface charge and stability along the time. Besides, ascorbic acid may be recognized by GLUTs receptors that are overexpressed in several kinds of tumoral cells. Therefore, MNPs-AA was selected to explore its performance in both MRI and in vitro assays using human colon cancer cells HCT 116. MRI experiments were performed in clinical equipment using a series of aqueous dispersions of MNPs-AA that were evaluated as T-2 contrast agent. The T-2- weighted images obtained as well as the calculated( )r2,( )indicated that MNPs-AA could act as efficient T-2 contrast agent for MRI. Regarding in vitro assays, MNPs-AA did not alter the cellular function neither exert cytotoxicity using the three explored doses. The internalization of the nanoparticles on the cellular structure was confirmed quanti and qualitatively using atomic absorption spectroscopy and Prussian blue techniques respectively. From these results, it emerges that ascorbic acid coated-magnetite nanoparticles may be used as alternative contrast agent to avoid or minimize some toxicological issues related to the widely used gadolinium.

Magnetic nanotheranostics were designed from iron oxide nanoparticles functionalized with folic acid (FA) and loaded with doxorubicin (Doxo) as a therapeutic agent. The incorporation of Doxo was carefully examined to attain a satisfactory drug loading efficiency. The magnet-guiding ability was examined in vitro. To achieve this, a novel continuous flow system was fabricated to quantify the amount of MNPs retained in the magnet site in an environment and under conditions mimicking the bloodstream. The obtained data suggest that almost 21% of the total circulating nanoparticles accumulated in the target site after 45 min of assay. Such amount ensured the doses of Doxo commonly employed during in vivo studies. The release of Doxo was analysed by implementing an original procedure devoted to simulate the pathways followed by MNPs once intravenously administered. From these studies, reliable data on the amount of drug that effectively reached the target site were obtained. The efficiency of the nanosystems as selective contrast agents in MRI was analysed using clinical 1.5 T equipment. Their potential as T₂ weighted contrast media was demonstrated. The data collected within this work appear as the former initial stage to validate the nanotheranostics before in vivo evaluation of this novel technology.

Magnetic resonance imaging is one of the most widely used diagnostic techniques, since it is non-invasive and provides high spatial resolution. Contrast agents (CAs) are usually required to improve the contrast capability. CAs can be classified as T1 (or positive) or T2 (or negative) contrast agents. Nowadays, gadolinium chelates (which generate T1 contrast) are the most used in clinical settings. However, the use of these chelates presents some drawbacks associated with their toxicity. Iron oxide magnetic nanoparticles (MNPs) have been extensively investigated as CA for MRI, especially for their capacity to generate negative contrast. The need for more efficient and safer contrast agents has focused investigations on the development of dual CAs, i.e., CAs that can generate both positive and negative contrast with a single administration. In this sense, nanotechnology appears as an attractive tool to achieve this goal. Nanoparticles can be modified not only to improve the contrast ability of the current CAs but also to enhance their biocompatibility, resolving toxicity issues. With the aim of contributing to the field of development of dual T1/T2 contrast agents for MRI, here, we present the obtained results of the synthesis of hybrid nanoparticles composed of magnetite/maghemite and gadolinium hydroxide. Exhaustive characterization work was conducted in order to understand how the hybrid nanoparticles were formed. The nanoparticles were extensively characterized through FTIR and UV–Vis spectroscopy, TEM and SEM microscopy, X-ray diffraction (XRD) analysis, dynamic light scattering, zeta potential, thermogravimetric analysis, energy-dispersive X-ray and vibrating-sample magnetometry. Stabilization studies were carried out to get an idea of the behavior of nanohybrids in physiological media. Special interest was given to the evaluation of Gd³⁺ leaching. It was found that carbohydrate coating as well as the adsorption of proteins on the surface may improve the stabilization of hybrid nanoparticles.

Morin is an antioxidant and anticancer flavonoid, extracted from natural sources, that may exert beneficial effects for several pathologies. Despite this, the administration of morin represents a challenge due to its low aqueous solubility. Mesoporous silica materials have emerged as biocompatible tools for drug delivery, as their pore size can be modulated for maximum surface area to volume ratio. In this contribution, we evaluate the ability of iron-modified mesoporous materials, for morin loading and controlled delivery. The SBA-15 and MCM-41 sieves were synthesized and modified with iron (metal content 4.02 and 6.27 % wt, respectivily). Characterization by transmission electron microscopy, XRD and UV-Vis revealed adequate pore size and agglomerates of very small metallic nanospecies (nanoclusters), without larger iron oxide nanoparticles. FT-IR spectra confirmed the presence of silanol groups in the solid hosts, which can interact with different groups present in morin molecules. SBA-15 materials were more efficient in terms of morin loading capacity (LC) due to their larger pore diameter. LC was more than 35% for SBA-15 materials when adsorptions studies were carried out with 9 mg of drug. Antioxidant activity were assayed by using DPPH test. Free iron materials presented a significate improvement as antioxidants after morin incorporation, reaching a scavenging activity of almost a 90%. On the other hand, in iron modified mesoporous materials, the presence of morin did not affect the scavenging activity. The results could be related with the formation of a complex between the flavonoid and the iron. Finally, biosafety studies using normal epithelial cells revealed that neither the loaded nor the unloaded materials exerted toxicity, even at doses of 1 mg/ml. These findings expand knowledge about mesoporous materials as suitable carriers of flavonoids with the aim of improving therapies for a wide range of pathologies.