Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

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

Articles in Press

Document Type : Original Article

Authors
Zahra Abroodi 1
Ronak Shabani 2
Zohreh Bagher 3, 4
Jamileh Sadat Mirsanei 1
Mehdi Mehdizadeh 2
1 Student Research Committee, Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
2 Reproductive Sciences and Technology Research Center, Department of Anatomical Sciences, Iran University of Medical Sciences, Tehran, Iran
3 ENT and Head and Neck Research Center and Department, The Five Senses Health Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
4 Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
10.22038/ijbms.2026.95909.20689
Abstract
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 (50 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 3.40±1.43 nm by TEM and a hydrodynamic peak at 6.53±1.71 nm by DLS, with excellent colloidal stability, crystallinity, and superparamagnetic-like properties. The USPIONs-OE-MSCs exhibited an intracellular iron content of 8.65±0.35 pg/cell. TEM revealed that exosomes derived from USPIONs-OE-MSCs (USPIONs-exosomes) had a mean diameter of 95.69±44.91 nm, whereas DLS showed a hydrodynamic peak at 121.5±33.89 nm. ICP-OES confirmed successful iron labeling (13.50±0.49 ng Fe/μg exosomal protein), and labeled exosomes produced a 32.6% signal reduction in in vitro T2-weighted MRI compared with unlabeled exosomes (P≤0.0001).
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.
Keywords
Exosomes
Magnetic Iron oxide nanoparticles
Magnetic resonance imaging
Mesenchymal stem cells
Olfactory mucosa
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 07 October 2026