title: Efficient MRI labeling of endothelial progenitor cells: design of thiolated surface stabilized superparamagnetic iron oxide nanoparticles.
abstract: The aim of this study was to design thiolated surface stabilized superparamagnetic iron oxide nanoparticles (TSS-SPIONs) for efficient internalization with high MRI sensitivity. TSS-SPIONs were developed by chelation between thiolated chitosan-thioglycolic acid (chitosan-TGA) hydrogel and iron ions (Fe(2+)/Fe(3+)). Likely, unmodified chitosan hydrogel SPIONs (UC-SPIONs) and uncoated SPIONs were used as control. Moreover, TSS-SPIONs were investigated regarding to their iron core size, hydrodynamic diameter, zeta potential, iron contents, molar relaxivities (r1 and r2), and cellular internalization. TSS-SPIONs demonstrated an iron oxide core diameter (crystallite size by XRD) of 3.1 ± 0.02 nm, a hydrodynamic diameter of 94 ± 20 nm, a zeta potential of +21 ± 5 mV, and an iron content of 3.6 ± 0.9 mg/mL. In addition, internalization of TSS-SPIONs into human endothelial progenitor cells (EPC) from umbilical cord blood was more than threefold and 17-fold higher in contrast to UC-SPIONs and SPIONs, respectively. With twofold lower incubation iron concentration of TSS-SPIONs, more than threefold higher internalization was achieved as compared to Resovist®. Also, cell viability of more than 90% was observed in the presence of TSS-SPIONs after 24h. The molar MR relaxivities (r2) value at 1.5 T was threefold higher than that of Resovist® and demonstrated that TSS-SPIONs have the potential as very effective T2 contrast-enhancement agent. According to these findings, TSS-SPIONs with efficient internalization, lower cytotoxicity, and high MRI sensitivity seem to be promising for cell tracking.
authors.affiliation: Department of Pharmaceutical Technology, University of Innsbruck, Innsbruck, Austria.
authors.forename: Gul
authors.initials: G
authors.lastname: Shahnaz
authors.forename: Christian
authors.initials: C
authors.lastname: Kremser
authors.forename: Andreas
authors.initials: A
authors.lastname: Reinisch
authors.forename: Anja
authors.initials: A
authors.lastname: Vetter
authors.forename: Flavia
authors.initials: F
authors.lastname: Laffleur
authors.forename: Deni
authors.initials: D
authors.lastname: Rahmat
authors.forename: Javed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Sarah
authors.initials: S
authors.lastname: Dünnhaupt
authors.forename: Willi
authors.initials: W
authors.lastname: Salvenmoser
authors.forename: Richard
authors.initials: R
authors.lastname: Tessadri
authors.forename: Ulrich
authors.initials: U
authors.lastname: Griesser
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D003287:Contrast Media / Q000737:chemistry / Q000633:toxicity; D003911:Dextrans / Q000737:chemistry / Q000633:toxicity; D042783:Endothelial Cells / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D020100:Hydrogels; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D013234:Stem Cells / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013997:Time Factors; D018675:Toxicity Tests
chemical_list: D003287:Contrast Media; D003911:Dextrans; D005290:Ferric Compounds; D020100:Hydrogels; D058185:Magnetite Nanoparticles; D013438:Sulfhydryl Compounds; C000499:ferric oxide; D048271:Chitosan; C065507:ferumoxides
keywords: Chitosan; MRI sensitivity; Stem cells; Superparamagnetic iron oxide nanoparticles (SPIONs) Internalization; Thiolated polymer