A Review on the Design of Carbon-Based Nanomaterials as MRI Contrast Agents.

The administration of magnetic resonance imaging (MRI) contrast agents (CAs) has been conducted since 1988 by clinicians to enhance the clarity and interpretability of MR images. CAs based on gadolinium chelates are the clinical standard used worldwide for the diagnosis of various pathologies, such as the detection of brain lesions, the visualization of blood vessels, and the assessment of soft tissue disorders. However, due to ongoing concerns associated with the safety of gadolinium-based contrast agents, considerable efforts have been directed towards developing contrast agents with better relaxivities, reduced toxicity, and eventually combined therapeutic modalities. In this context, grafting (or encapsulating) paramagnetic metals or chelates onto (within) carbon-based nanoparticles is a straightforward approach enabling the production of contrast agents with high relaxivities while providing extensive tuneability regarding the functionalization of the nanoparticles. Here, we provide an overview of the parameters defining the efficacy of lanthanide-based contrast agents and the subsequent developments in the field of nanoparticular-based contrast agents incorporating paramagnetic species.

Comparison of MRI Properties between Multimeric DOTAGA and DO3A Gadolinium-Dendron Conjugates.

The inherent lack of sensitivity of MRI needs the development of new Gd contrast agents in order to extend the application of this technique to cellular imaging. For this purpose, two multimeric MR contrast agents obtained by peptidic coupling between an amido amine dendron and GdDOTAGA chelates (premetalation strategy, G1-4GdDOTAGA) or DO3A derivatives which then were postmetalated (G1-4GdDO3A) have been prepared. By comparison to the monomers, an increase of longitudinal relaxivity has been observed for both structures. Especially for G1-4GdDO3A, a marked increase is observed between 20 and 60 MHz. This structure differs from G1-4GdDOTAGA by an increased rigidity due to the aromatic linker between each chelate and the organic framework. This has the effect of limiting local rotational movements, which has a positive impact on relaxivity.

Superparamagnetic Iron Oxide Nanoparticles (SPION): From Fundamentals to State-of-the-Art Innovative Applications for Cancer Therapy.

Despite significant advances in cancer therapy over the years, its complex pathological process still represents a major health challenge when seeking effective treatment and improved healthcare. With the advent of nanotechnologies, nanomedicine-based cancer therapy has been widely explored as a promising technology able to handle the requirements of the clinical sector. Superparamagnetic iron oxide nanoparticles (SPION) have been at the forefront of nanotechnology development since the mid-1990s, thanks to their former role as contrast agents for magnetic resonance imaging. Though their use as MRI probes has been discontinued due to an unfavorable cost/benefit ratio, several innovative applications as therapeutic tools have prompted a renewal of interest. The unique characteristics of SPION, i.e., their magnetic properties enabling specific response when submitted to high frequency (magnetic hyperthermia) or low frequency (magneto-mechanical therapy) alternating magnetic field, and their ability to generate reactive oxygen species (either intrinsically or when activated using various stimuli), make them particularly adapted for cancer therapy. This review provides a comprehensive description of the fundamental aspects of SPION formulation and highlights various recent approaches regarding in vivo applications in the field of cancer therapy.

Advances in the Mechanistic Understanding of Iron Oxide Nanoparticles' Radiosensitizing Properties.

Among the plethora of nanosystems used in the field of theranostics, iron oxide nanoparticles (IONPs) occupy a central place because of their biocompatibility and magnetic properties. In this study, we highlight the radiosensitizing effect of two IONPs formulations (namely 7 nm carboxylated IONPs and PEG5000-IONPs) on A549 lung carcinoma cells when exposed to 225 kV X-rays after 6 h, 24 h and 48 h incubation. The hypothesis that nanoparticles exhibit their radiosensitizing effect by weakening cells through the inhibition of detoxification enzymes was evidenced by thioredoxin reductase activity monitoring. In particular, a good correlation between the amplification effect at 2 Gy and the residual activity of thioredoxin reductase was observed, which is consistent with previous observations made for gold nanoparticles (NPs). This emphasizes that NP-induced radiosensitization does not result solely from physical phenomena but also results from biological events.

Impact of the chain length on the biodistribution profiles of PEGylated iron oxide nanoparticles: a multimodal imaging study.

Bimodal sub-5 nm superparamagnetic iron oxide nanoparticles (SPIO-5) coated with polyethylene glycol of different chain lengths (i.e. PEG-800, -2000 and -5000) have been prepared and characterized. Fluorescence properties have been obtained by mean of the grafting of a near-infrared-emitting dye (NIR-dye) onto the surface of the oxide, thanks to the carboxylic acid functions introduced towards an organosilane coating. Such modification allowed us to follow in vivo their biodistribution and elimination pathways by T1-w and T2-w high-field magnetic resonance imaging (MRI), as well as by optical and optoacoustic imaging. Interestingly, it has been highlighted that for a given composition, the thickness of the coating strongly influences the pharmacokinetic properties of the administrated SPIO-5.

Influence of Experimental Parameters of a Continuous Flow Process on the Properties of Very Small Iron Oxide Nanoparticles (VSION) Designed for T1-Weighted Magnetic Resonance Imaging (MRI).

This study reports the development of a continuous flow process enabling the synthesis of very small iron oxide nanoparticles (VSION) intended for T1-weighted magnetic resonance imaging (MRI). The influence of parameters, such as the concentration/nature of surfactants, temperature, pressure and the residence time on the thermal decomposition of iron(III) acetylacetonate in organic media was evaluated. As observed by transmission electron microscopy (TEM), the diameter of the resulting nanoparticle remains constant when modifying the residence time. However, significant differences were observed in the magnetic and relaxometric studies. This continuous flow experimental setup allowed the production of VSION with high flow rates (up to 2 mL·min-1), demonstrating the efficacy of such process compared to conventional batch procedure for the scale-up production of VSION.

Magnetic iron oxide nanoparticles for drug delivery: applications and characteristics.

INTRODUCTION: For many years, the controlled delivery of therapeutic compounds has been a matter of great interest in the field of nanomedicine. Among the wide amount of drug nanocarriers, magnetic iron oxide nanoparticles (IONs) stand out from the crowd and constitute robust nanoplatforms since they can achieve high drug loading as well as targeting abilities stemming from their remarkable properties (magnetic and biological properties). These applications require precise design of the nanoparticles regarding several parameters which must be considered together in order to attain highest therapeutic efficacy. AREAS COVERED: This short review presents recent developments in the field of cancer targeted drug delivery using magnetic nanocarriers as drug delivery systems. EXPERT OPINION: The design of nanocarriers enabling efficient delivery of therapeutic compounds toward targeted locations is one of the major area of research in the targeted drug delivery field. By precisely shaping the structural properties of the iron oxide nanoparticles, drugs loaded onto the nanoparticles can be efficiently guided and selectively delivered toward targeted locations. With these goals in mind, special attention should be given to the pharmacokinetics and in vivo behavior of the developed nanocarriers.