Morphology Effect of PEGylated Iron Oxide Nanoparticles on the Enhancement of MRI Contrast Signal in Breast Cancer.

MRI is one of the most powerful imaging modalities to diagnose cancer at early stages, which can be further improved with contrast agents (CAs). For this purpose, iron oxide nanoparticles (IONs) are commonly used as T(2) probes to enhance the contrast in MRI scans. The morphology of IONs plays an important role in determining their contrast abilities when exposed to external magnetic fields, yet the underlying mechanism remains elusive. To better understand the relationship of T(2) relaxation with anisotropic-shaped IONs (ASIONs), we produced PEG-IONs with similar core geometrical volumes and different morphologies─spheres (SIONs), cubes (CIONs), and rhombohedra (RIONs). We then compared their effectiveness as MRI CAs to commercially available ferumoxytol (FMX) through physicochemical studies (TEM, FTIR, XRD, DLS), magnetic analyses (VSM, magnetic relaxation), phantom imaging, in vitro studies (CCK-8), and in vivo studies (biodistribution, blood circulation, and MR imaging) using a T11 breast cancer animal model. The ASIONs proved to have well-defined morphologies, be colloidally stable over 24 h, nontoxic to breast cancer cells, and exhibit superior magnetic response and relaxivities compared to FMX. We found that the morphology of IONs can determine the effective radius (r*), stray field gradient, and local field inhomogeneity, which elicit subsequent changes in the transverse relaxation rate of water protons within T11 tumor microenvironments. RIONs exhibited the greatest negative contrast enhancement with almost 70% retention in the blood after 1 h, correlating well with the outer sphere theory and their greater r*, indicating they can be used as potent and more effective CAs in breast cancer imaging. This study has the potential to dictate basic criteria for designing high-performance probes for the early detection of noncommunicable diseases.