Iron Oxide Colloidal Nanoclusters as Theranostic Vehicles and Their Interactions at the Cellular Level

Abstract

Advances in surfactant-assisted chemical approaches have led the way for the exploitation of nanoscale inorganic particles in medical diagnosis and treatment. In this field, magnetically-driven multimodal nanotools that perform both detection and therapy, well-designed in size, shape and composition, are highly advantageous. Such a theranostic material—which entails the controlled assembly of smaller (maghemite) nanocrystals in a secondary motif that is highly dispersible in aqueous media—is discussed here. These surface functionalized, pomegranate-like ferrimagnetic nanoclusters (40–85 nm) are made of nanocrystal subunits that show a remarkable magnetic resonance imaging contrast efficiency, which is better than that of the superparamagnetic contrast agent Endorem©. Going beyond this attribute and with their demonstrated low cytotoxicity in hand, we examine the critical interaction of such nanoprobes with cells at different physiological environments. The time-dependent in vivo scintigraphic imaging of mice experimental models, combined with a biodistribution study, revealed the accumulation of nanoclusters in the spleen and liver. Moreover, the in vitro proliferation of spleen cells and cytokine production witnessed a size-selective regulation of immune system cells, inferring that smaller clusters induce mainly inflammatory activities, while larger ones induce anti-inflammatory actions. The preliminary findings corroborate that the modular chemistry of magnetic iron oxide nanoclusters stimulates unexplored pathways that could be driven to alter their function in favor of healthcare.

How the Physicochemical Properties of Manufactured Nanomaterials Affect Their Performance in Dispersion and Their Applications in Biomedicine: A Review

“…When surface-functionalized pomegranate-like ferrimagnetic nanoclusters (40–85 nm) were used in vitro, it was shown that the proliferation of spleenocytes, as well as the cytokine production, were consistent with the regulation of immune system cells based on size; it was inferred that small clusters mainly drive immune-stimulatory and inflammatory responses, while large ones could lead to immune-suppressive and anti-inflammatory actions [ 197 ].…”

Preparation and Application of Iron Oxide Nanoclusters

“…Because of their larger sizes, these capsules were sensitive to ultrasound, which enhanced drug localization at the tumor site with ultrasound treatment (Figure 9d). T2 MRI contrast agents are mainly superparamagnetic nanoparticles, and nanocluster formation increases the magnetic signal and subsequently enhances the imaging sensitivity or cell labeling efficiency [24,30,52,53,56,[65][66][67]. For example, differently sized iron oxide nanoclusters via solvothermal synthesis showed higher r2 relaxivity for nanocluster sizes of around 50-60 nm.…”

Solvothermal Synthesis Combined with Design of Experiments—Optimization Approach for Magnetite Nanocrystal Clusters

“…When the field is removed, thermal motion randomizes the alignment of the magnetic moment and the particles show no magnetic behavior anymore. These nanoparticles are known to be ideal candidates for medicinal applications, for example, as MRI negative contrast agents [ 10 , 11 ], in cancer therapy [ 12 , 13 ], hyperthermia therapy [ 14 , 15 , 16 ], and diagnostics [ 17 , 18 ], or for targeted drug delivery [ 19 , 20 ]. The small size of these superparamagnetic particles can, nonetheless, also be a disadvantage, depending on the desired application.…”