title: Effect of PEG molecular weight on stability, T₂ contrast, cytotoxicity, and cellular uptake of superparamagnetic iron oxide nanoparticles (SPIONs).
abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) are currently unavailable as MRI contrast agents for detecting atherosclerosis in the clinical setting because of either low signal enhancement or safety concerns. Therefore, a new generation of SPIONs with increased circulation time, enhanced image contrast, and less cytotoxicity is essential. In this study, monodisperse SPIONs were synthesized and coated with polyethylene glycol (PEG) of varying molecular weights. The resulting PEGylated SPIONs were characterized, and their interactions with vascular smooth muscle cells (VSMCs) were examined. SPIONs were tested at different concentrations (100 and 500 ppm Fe) for stability, T2 contrast, cytotoxicity, and cellular uptake to determine an optimal formulation for in vivo use. We found that at 100 ppm Fe, the PEG 2K SPIONs showed adequate stability and magnetic contrast, and exhibited the least cytotoxicity and nonspecific cellular uptake. An increase in cell viability was observed when the SPION-treated cells were washed with PBS after 1h incubation compared to 5 and 24h incubation without washing. Our investigation provides insight into the potential safe application of SPIONs in the clinic.
authors.affiliation: Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, MA 02215, USA.
authors.forename: Yoonjee C
authors.initials: YC
authors.lastname: Park
authors.affiliation: Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, MA 02215, USA.
authors.forename: Jared B
authors.initials: JB
authors.lastname: Smith
authors.affiliation: Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, MA 02215, USA.
authors.forename: Tuan
authors.initials: T
authors.lastname: Pham
authors.affiliation: Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, MA 02215, USA.
authors.forename: Ragnhild D
authors.initials: RD
authors.lastname: Whitaker
authors.affiliation: Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, MA 02215, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Sucato
authors.affiliation: Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, MA 02215, USA; Department of Physiology and Biophysics, Boston University School of Medicine, 700 Albany Street, Boston, MA 02118, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Hamilton
authors.affiliation: Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, MA 02215, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bartolak-Suki
authors.affiliation: Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, MA 02215, USA. Electronic address: JYWONG@BU.EDU.
authors.forename: Joyce Y
authors.initials: JY
authors.lastname: Wong
mesh_terms: D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology*; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology*; D052203:Ferrosoferric Oxide / Q000737:chemistry; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D020099:Coated Materials, Biocompatible; D003287:Contrast Media; D058185:Magnetite Nanoparticles; D011092:Polyethylene Glycols; D052203:Ferrosoferric Oxide
keywords: Coating; Particle internalization; Stability; Superparamagnetic iron oxide nanoparticles; T(2) relaxation; Toxicity