Citrate-coated ultrasmall superparamagnetic iron oxide nanoparticles for efficient labeling and MRI tracking of olfactory ectomesenchymal stem cell-derived exosomes

Objective(s): Exosomes are promising nanoscale carriers for cell-free regenerative medicine; however, limited in vivo traceability and inefficient targeting hinder their clinical translation. We investigated the feasibility of using citrate-coated ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) to efficiently label and MRI-track stem cell-derived exosomes. Materials and Methods: USPIONs were synthesized and characterized using TEM (transmission electron microscopy) and DLS (dynamic light scattering), with complementary physicochemical characterization techniques. Olfactory ectomesenchymal stem cells (OE-MSCs) were labeled with USPIONs (۵۰ μg/ml), and labeling efficiency was evaluated using cell viability assay, intracellular iron quantification, Prussian blue staining, and TEM. Exosomes were isolated from the USPIONs-labeled OE-MSCs (USPIONs-OE-MSCs) and characterized. All quantitative measurements were performed in triplicate, and data are presented as mean±SD.Results: USPIONs exhibited a mean core size of ۳.۴۰±۱.۴۳ nm by TEM and a hydrodynamic peak at ۶.۵۳±۱.۷۱ nm by DLS, with excellent colloidal stability, crystallinity, and superparamagnetic-like properties. The USPIONs-OE-MSCs exhibited an intracellular iron content of ۸.۶۵±۰.۳۵ pg/cell. TEM revealed that exosomes derived from USPIONs-OE-MSCs (USPIONs-exosomes) had a mean diameter of ۹۵.۶۹±۴۴.۹۱ nm, whereas DLS showed a hydrodynamic peak at ۱۲۱.۵±۳۳.۸۹ nm. ICP-OES confirmed successful iron labeling (۱۳.۵۰±۰.۴۹ ng Fe/μg exosomal protein), and labeled exosomes produced a ۳۲.۶% signal reduction in in vitro T۲-weighted MRI compared with unlabeled exosomes (P≤۰.۰۰۰۱).Conclusion: USPIONs provide an efficient, biocompatible platform for exosome labeling, enabling MRI-based tracking. This strategy may facilitate exosome engineering for regenerative nanomedicine and targeted delivery.

کلیدواژه ها:

Exosomes ، Magnetic Iron Oxide Nanoparticles ، magnetic resonance imaging ، Mesenchymal stem cells ، Olfactory mucosa