Dextran-coated superparamagnetic iron oxide nanoparticles for magnetic resonance imaging: evaluation of size-dependent imaging properties, storage stability and safety

TLDR

Criticism of current MRI contrast agents for side effects or limited functional imaging has driven the need for safer, more versatile agents, and we previously showed dextran‑coated superparamagnetic iron oxide nanoparticles (SPION Dex) are safe and biocompatible. The study investigates how particle size affects cross‑linking and imaging properties of SPION Dex. We measured relaxivity with a simple experiment and assessed storage stability at various temperatures over 12 weeks, finding no agglomeration or sedimentation. SPION Dex showed no irritation in a chick chorioallantoic membrane assay, were taken up by macrophages but not non‑phagocytic cells, did not trigger CARPA in pigs, and remained stable over 12 weeks, underscoring their exceptional safety. Keywords: CARPA, cross‑linking, irritation potential, MRI, SPION, storage stability.

Abstract

Background: Rising criticism of currently available contrast agents for magnetic resonance imaging, either due to their side effects or limited possibilities in terms of functional imaging, evoked the need for safer and more versatile agents. We previously demonstrated the suitability of novel dextran-coated superparamagnetic iron oxide nanoparticles (SPION Dex ) for biomedical applications in terms of safety and biocompatibility. Methods: In the present study, we investigated the size-dependent cross-linking process of these particles as well as the size dependency of their imaging properties. For the latter purpose, we adopted a simple and easy-to-perform experiment to estimate the relaxivity of the particles. Furthermore, we performed an extensive analysis of the particles’ storage stability under different temperature conditions, showing their superb stability and the lack of any signs of agglomeration or sedimentation during a 12 week period. Results: Independent of their size, SPION Dex displayed no irritation potential in a chick chorioallantoic membrane assay. Cell uptake studies of ultra-small (30 nm) SPION Dex confirmed their internalization by macrophages, but not by non-phagocytic cells. Additionally, complement activation-related pseudoallergy (CARPA) experiments in pigs treated with ultra-small SPION Dex indicated the absence of hypersensitivity reactions. Conclusion: These results emphasize the exceptional safety of SPION Dex , setting them apart from the existing SPION-based contrast agents and making them a very promising candidate for further clinical development. Keywords: CARPA, cross-linking, irritation potential, MRI, SPION, storage stability