Nano-confinement-driven enhanced magnetic relaxivity of SPIONs for targeted tumor bioimaging

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) are highly biocompatible and have a versatile synthetic technique based on coprecipitation, reduction-precipitation, and hydrothermal methods, where Fe and Fe react in aqueous solutions; both these ions are present in our body and have clear metabolic pathways; therefore, they have attracted extensive research interest and development in the field of diagnostic imaging and therapy. However, most SPION-based clinical diagnostic contrast agents are discontinued due to severe pain, low transverse magnetic relaxivity range of 80-180 mM s, shorter circulation half-life, and lack of disease specificity. Therefore, in this study, we engineered a bone cancer-targeted hybrid nanoconstruct (HNC) with a high transverse magnetic relaxivity of 625 mM s, which was significantly higher than that of clinical contrast agents. The engineered HNC is peripherally decorated with a bone-seeking agent, alendronic acid-conjugated phospholipid, exhibiting a hydrodynamic size of 80 nm with a negative surface potential, -35 mV. The interior skeleton of the HNC is composed of biodegradable and biocompatible poly(l-lactic-co-glycolic acid) (PLGA), in which 5 nm SPIONs are confined. We have successfully tuned the distance between the confined SPIONs from 0.5 to 4 nm, as revealed by transmission electron microscopy (TEM) images and magnetic resonance image (MRI) phantoms. This cluster confinement dramatically enhances magnetic relaxivity possibly due to the increase in net local magnetization due to proximal field inhomogeneity. In an in vitro examination, 80% of HNC is found to bind with hydroxyapatite (HAp), which when characterized by TEM shows a painting of SPIONs over a HAp crystal. HNC is found to accumulate in mouse osteosarcoma tumor (K7M2 tumor model); both MRI and histological examination of the tumor show the potential of HNC as targeting agents for diagnosis of tumor in the bone.

Structure–Relaxivity Relationships of Magnetic Nanoparticles for Magnetic Resonance Imaging

“…This study shed light on interpreting the relationship between the T 2 relaxivity and the magnetic field inhomogeneity induced by MNPs, especially in MNP clusters. [193][194] Previously, Mikhaylov et al reported that ferri-liposomes consisting of spherical IO NPs with widely dispersed diameters (i.e., ranging from 3 to 14 nm) exhibited ultrahigh r 2 value up to 1286 mM −1 s −1 by an unknown mechanism. [195] We speculate that this result may be a consequence of enhanced magnetic field inhomogeneity derived from the large size deviations of IO NPs used for fabricating the ferri-liposomes.…”

Dy-DOTA integrated mesoporous silica nanoparticles as promising ultrahigh field magnetic resonance imaging contrast agents

“…Similar effects have been noted in loading a high level of ultra-small SPIONs within polymeric nanoparticles. 36 However, this work represents the first example, to the best of our knowledge, of a paramagnetic contrast agent where Curie spin relaxation and outer-sphere effects dominate. This study not only illustrates the distinct mechanistic aspects of Dy-based agents, but also provides a general strategy to efficiently improve the r2 relaxivity under high field.…”

Integration of gadolinium in nanostructure for contrast enhanced‐magnetic resonance imaging

“…Among the contrast agents, MRI CAs are safer when compared to those used in X-ray/CT scans and nuclear medicine. The commonly used CAs in Ce-MRI includes Gd 3+ , Mn 2+ , and Fe 3+ complexes Thanh Nguyen, Pitchaimani, Ferrel, Thakkar, & Aryal, 2018;Wahsner et al, 2018;Wang et al, 2018). Among these CAs, the majority of Ce-MRI is attributed to GBCAs due to their bright contrast due to its high magnetic moment, better thermodynamic, and kinetic stability in-vivo (Gizzatov et al, 2014;Schroeder, Clarke, Neubauer, & Tyler, 2011).…”