Pheomelanin and PEG Coatings on Superparamagnetic Fe ₃ O ₄ Nanoparticles: Reduced T ₂ in MRI for Early Cancer Diagnosis

High Resolution Image Download MS PowerPoint Slide Nanotechnology is a field that is widely accepted as improving breast cancer diagnosis and making it safer from a clinical perspective. The use of superparamagnetic iron oxide nanoparticles as negative contrast agents (SPION-CAs) can be a favorable alternative to gadolinium-based contrast agents (Gd-CAs) because the latter can cause nephrogenic systemic fibrosis in patients with renal impairment. The main advantages of SPION-CAs over Gd-CAs are their biocompatibility, including low cytotoxicity, long blood circulation times, and efficient elimination through natural metabolic pathways or via storage and degradation of iron oxide (ferritinophagy). Recently, ultrasmall SPION-CAs coated with polyethylene glycol (PEG) for vascular imaging were approved in China. In this work, we synthesized PEG-coated SPIONs (SPION-A01) and compared them with pheomelanin-coated SPIONs (SPION-C01), as pheomelanin is a biocompatible bio-oligomer with a high affinity for iron coordination sites. Analyses by TEM and XRD showed an average core diameter of approximately 6.0 nm (SPION-A01) and 10.0 nm (SPION-C01), and superparamagnetic behavior was expected. VSM measurement confirmed this prediction, with SPION-C01 exhibiting a saturation magnetization approximately twice that of SPION-A01. Zeta-potential measurements indicated good colloidal stability of the samples, with SPION-C01 showing higher stability than SPION-A01. Indeed, the DLS analysis showed that SPION-C01 is thinner than SPION-A01, which is consistent with the presence of pheomelanin monomeric units. The in vitro assays, such as cytotoxicity, Prussian blue staining, and TEM (analysis in MCF-7 cells), showed their low cytotoxicity and positive uptake in human breast carcinoma (MCF-7) and normal fibroblast cells (McCoy). Moreover, the ex vivo hemolytic activity assay showed that both samples were negative, confirming their hemocompatibility. Indeed, the in vitro MRI measurements showed that the transverse relaxivity values ( r 2 ), which measure the MRI efficiency, were similar for both samples, but SPION-C01 exhibited a slightly higher r 2, supporting its potential as a negative SPION-CA.