Biocompatible superparamagnetic core-shell nanoparticles for potential use in hyperthermia-enabled drug release and as an enhanced contrast agent.

Superparamagnetic iron oxide nanoparticles (SPIONs) and core-shell type nanoparticles, consisting of SPIONs coated with mesoporous silica and/or lipid, were synthesised and tested for their potential theranostic applications in drug delivery, magnetic hyperthermia and as a contrast agent. Transmission Electron Microscopy (TEM) confirmed the size of bare and coated SPIONs was in the range of 5-20 nm and 100-200 nm respectively. The superparamagnetic nature of all the prepared nanomaterials as indicated by Vibrating Sample Magnetometry (VSM) and their heating properties under an AC field confirm their potential for hyperthermia applications. Scanning Column Magnetometry (SCM) data showed that extrusion of bare-SPION (b-SPION) dispersions through a 100 nm polycarbonate membrane significantly improved the dispersion stability of the sample. No sedimentation was apparent after 18 h compared to a pre-extrusion estimate of 43% settled at the bottom of the tube over the same time. Lipid coating also enhanced dispersion stability. Transversal relaxation time (T2) measurements for the nanoparticles, using a bench-top relaxometer, displayed a significantly lower value of 46 ms, with a narrow relaxation time distribution, for lipid silica coated SPIONs (Lip-SiSPIONs) as compared to that of 1316 ms for the b-SPIONs. Entrapment efficiency of the anticancer drug, Doxorubicin (DOX) for Lip-SPIONs was observed to be 35% which increased to 58% for Lip-SiSPIONs. Moreover, initial in-vitro cytotoxicity studies against human breast adenocarcinoma, MCF-7 cells showed that % cell viability increased from 57% for bSPIONs to 82% for Lip-SPIONs and to 87% for Lip-SiSPIONs. This suggests that silica and lipid coatings improve the biocompatibility of bSPIONs significantly and enhance the suitability of these particles as drug carriers. Hence, the magnetic nanomaterials prepared in this work have potential theranostic properties as a drug carrier for hyperthermia cancer therapy and also offer enhancement of contrast agent efficacy and a route to a significant increase in dispersion stability.

Effect of crosslinking agent to design nanostructured hyaluronic acid-based hydrogels with improved relaxometric properties.

Nowadays, natural polysaccharides have given promising results as drug carriers. Among them, the hydrogels, thanks to their versatile properties, have been produced and engineered at the nano-scale in order to develop nanovectors for diagnostic and therapeutic purposes. Here, we investigate the contribution that a natural biopolymer, hyaluronic acid (HA), can give to the field of Magnetic Resonance Imaging (MRI). In addition, we study the relaxometric properties of crosslinked and non-crosslinked hydrogel networks and outline the impact of both HA concentration and crosslinker, Divinyl Sulfone (DVS), on the relaxivity of aqueous polymer solutions, even in the absence of Contrast Agents (CAs). Results show that proper HA concentration and the presence of the crosslinking agent can enhance the longitudinal relaxation time of the surrounding water, even in the absence of CAs. These findings could inspire the design of novel nanostructured hydrogels with enhanced relaxometric properties for MRI applications and not only.

Water-Mediated Nanostructures for Enhanced MRI: Impact of Water Dynamics on Relaxometric Properties of Gd-DTPA.

Recently, rational design of a new class of contrast agents (CAs), based on biopolymers (hydrogels), have received considerable attention in Magnetic Resonance Imaging (MRI) diagnostic field. Several strategies have been adopted to improve relaxivity without chemical modification of the commercial CAs, however, understanding the MRI enhancement mechanism remains a challenge. Methods: A multidisciplinary approach is used to highlight the basic principles ruling biopolymer-CA interactions in the perspective of their influence on the relaxometric properties of the CA. Changes in polymer conformation and thermodynamic interactions of CAs and polymers in aqueous solutions are detected by isothermal titration calorimetric (ITC) measurements and later, these interactions are investigated at the molecular level using NMR to better understand the involved phenomena. Water molecular dynamics of these systems is also studied using Differential Scanning Calorimetry (DSC). To observe relaxometric properties variations, we have monitored the MRI enhancement of the examined structures over all the experiments. The study of polymer-CA solutions reveals that thermodynamic interactions between biopolymers and CAs could be used to improve MRI Gd-based CA efficiency. High-Pressure Homogenization is used to obtain nanoparticles. Results: The effect of the hydration of the hydrogel structure on the relaxometric properties, called Hydrodenticity and its application to the nanomedicine field, is exploited. The explanation of this concept takes place through several key aspects underlying biopolymer-CA's interactions mediated by the water. In addition, Hydrodenticity is applied to develop Gadolinium-based polymer nanovectors with size around 200 nm with improved MRI relaxation time (10-times). Conclusions: The experimental results indicate that the entrapment of metal chelates in hydrogel nanostructures offers a versatile platform for developing different high performing CAs for disease diagnosis.