title: Enhanced cellular uptake of aminosilane-coated superparamagnetic iron oxide nanoparticles in mammalian cell lines.
abstract: OBJECTIVE
  To compare the cellular uptake efficiency and cytotoxicity of aminosilane (SiO(2)-NH(2))-coated superparamagnetic iron oxide (SPIO@SiO(2)-NH(2)) nanoparticles with three other types of SPIO nanoparticles coated with SiO(2) (SPIO@SiO(2)), dextran (SPIO@dextran), or bare SPIO in mammalian cell lines.
  
  
  METHODS
  Four types of monodispersed SPIO nanoparticles with a SPIO core size of 7 nm and an overall size in a range of 7-15 nm were synthesized. The mammalian cell lines of MCF-7, MDA-MB-231, HT-29, RAW264.7, L929, HepG2, PC-3, U-87 MG, and mouse mesenchymal stem cells (MSCs) were incubated with four types of SPIO nanoparticles for 24 hours in the serum-free culture medium Dulbecco's modified Eagle's medium (DMEM) with 4.5 μg/mL iron concentration. The cellular uptake efficiencies of SPIO nanoparticles were compared by Prussian blue staining and intracellular iron quantification. In vitro magnetic resonance imaging of MSC pellets after SPIO labeling was performed at 3 T. The effect of each SPIO nanoparticle on the cell viability of RAW 264.7 (mouse monocyte/macrophage) cells was also evaluated.
  
  
  RESULTS
  Transmission electron microscopy demonstrated surface coating with SiO(2)-NH(2), SiO(2), and dextran prevented SPIO nanoparticle aggregation in DMEM culture medium. MCF-7, MDA-MB-231, and HT-29 cells failed to show notable iron uptake. For all the remaining six cell lines, Prussian blue staining and intracellular iron quantification demonstrated that SPIO@ SiO(2)-NH(2) nanoparticles had the highest cellular uptake efficiency. SPIO@SiO(2)-NH(2), bare SPIO, and SPIO@dextran nanoparticles did not affect RAW 264.7 cell viability up to 200 μg Fe/mL, while SPIO@SiO(2) reduced RAW 264.7 cell viability from 10 to 200 μg Fe/mL in a dose-dependent manner.
  
  
  CONCLUSIONS
  Cellular uptake efficiency of SPIO nanoparticles depends on both the cell type and SPIO surface characteristics. Aminosilane surface coating enhanced the cellular uptake efficiency without inducing cytotoxicity in a number of cell lines.
authors.affiliation: Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Zhu
authors.forename: Yi-Xiang J
authors.initials: YX
authors.lastname: Wang
authors.forename: Ken Cham-Fai
authors.initials: KC
authors.lastname: Leung
authors.forename: Siu-Fung
authors.initials: SF
authors.lastname: Lee
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Wang
authors.forename: Josie M Y
authors.initials: JM
authors.lastname: Lai
authors.forename: Chao
authors.initials: C
authors.lastname: Wan
authors.forename: Christopher H K
authors.initials: CH
authors.lastname: Cheng
authors.forename: Anil T
authors.initials: AT
authors.lastname: Ahuja
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005290:Ferric Compounds / Q000737:chemistry* / Q000493:pharmacokinetics*; D005295:Ferrocyanides; D006651:Histocytochemistry; D006801:Humans; D042541:Intracellular Space / Q000737:chemistry; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D011437:Propylamines; D012821:Silanes / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D005290:Ferric Compounds; D005295:Ferrocyanides; D058185:Magnetite Nanoparticles; D011437:Propylamines; D012821:Silanes; C000499:ferric oxide; C040733:tetraethoxysilane; C477625:amino-propyl-triethoxysilane; C000170:ferric ferrocyanide