title: Evaluation of biocompatible alginate- and deferoxamine-coated ternary composites for magnetic resonance imaging and gene delivery into glioblastoma cells.
abstract: BACKGROUND
  This paper describes comparative studies in cytotoxicities, magnetic resonance imaging (MRI), and gene delivery into glioblastoma U87MG or U138MG cells with ternary composites that are consist of superparamagnetic iron oxide (SPIO) nanoparticles (NPs) (size: 8-10 nm) with different surface coatings, circular plasmid DNA (pDNA) (~4 kb) equipped with fluorescent/luminescent probe, and branched polyethylenimine (25 kDa, PDI 2.5).
  
  
  METHODS
  Three types of SPIO-NPs were used, including: (I) naked iron oxide NPs with Fe-OH surface group (Bare-NP); (II) iron oxide NPs with a coating of alginate (Alg-NPs); and (III) iron oxide NPs with a coating of deferoxamine (Def-NPs). By tuning the polyethylenimine (PEI)/NP ratios and with a fixed DNA amount, different ternary composites were employed for NP/gene transfection into glioblastoma U87MG or U138MG cells, which were then characterized by Prussian blue staining, in vitro MRI, green fluorescence protein (GFP) fluorescence and luciferase assay.
  
  
  RESULTS
  Among the composites prepared, 0.2 ng PEI/0.5 µg DNA/1.0 µg Bare-NP ternary composite possessed the best cellular uptake efficiency of NP to the cytoplasm, following the trend Bare-NP > Alg-NP > Def-NP. This observation was consistent to the MRI assessments with in vitro T 2 relaxivity (r 2) values of 46.0, 35.5, and 23.7 s(-1)·µM(-1)·Fe, respectively. For cellular uptake efficiency of the pDNA, all variations of PEI/NP ratios of the composites did not yield significant differences. However, cellular uptake efficiencies of pDNA in the ternary composites in U138MG cells were generally higher than that of U87MG cells by an order of magnitude. Exceptionally, the ternary composite 0.2 ng PEI/0.5 µg DNA/1.0 µg Bare-NP possessed a lowered luciferase activity RLU for gene expression in U138MG cells. A total of 0.2 ng PEI/0.5 µg DNA/0.1 µg Bare-NP would be uptaken to the cell nucleus with the highest luciferase activity. A working concentration range of PEI with at least 15% higher cell viabilities than lipofectamine was 0.1 to 0.2 ng/well. The cytotoxicities became significant when 0.5 ng/well PEI was present in the ternary composites.
  
  
  CONCLUSIONS
  The as-prepared composites offer potential biomedical applications in simultaneous gene delivery, imaging contrast enhancement, and metabolism study.
authors.affiliation: 1 Department of Chemistry, Institute of Creativity and Partner State Key Laboratory of Environmental and Biological Analysis, The Hong Kong Baptist University, Hong Kong SAR, China ; 2 School of Biomedical Sciences and Center of Novel Functional Molecules, 3 Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China ; 4 Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Ken Cham-Fai
authors.initials: KC
authors.lastname: Leung
authors.affiliation: 1 Department of Chemistry, Institute of Creativity and Partner State Key Laboratory of Environmental and Biological Analysis, The Hong Kong Baptist University, Hong Kong SAR, China ; 2 School of Biomedical Sciences and Center of Novel Functional Molecules, 3 Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China ; 4 Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Kathy W Y
authors.initials: KW
authors.lastname: Sham
authors.affiliation: 1 Department of Chemistry, Institute of Creativity and Partner State Key Laboratory of Environmental and Biological Analysis, The Hong Kong Baptist University, Hong Kong SAR, China ; 2 School of Biomedical Sciences and Center of Novel Functional Molecules, 3 Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China ; 4 Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Chun-Pong
authors.initials: CP
authors.lastname: Chak
authors.affiliation: 1 Department of Chemistry, Institute of Creativity and Partner State Key Laboratory of Environmental and Biological Analysis, The Hong Kong Baptist University, Hong Kong SAR, China ; 2 School of Biomedical Sciences and Center of Novel Functional Molecules, 3 Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China ; 4 Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Josie M Y
authors.initials: JM
authors.lastname: Lai
authors.affiliation: 1 Department of Chemistry, Institute of Creativity and Partner State Key Laboratory of Environmental and Biological Analysis, The Hong Kong Baptist University, Hong Kong SAR, China ; 2 School of Biomedical Sciences and Center of Novel Functional Molecules, 3 Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China ; 4 Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Siu-Fung
authors.initials: SF
authors.lastname: Lee
authors.affiliation: 1 Department of Chemistry, Institute of Creativity and Partner State Key Laboratory of Environmental and Biological Analysis, The Hong Kong Baptist University, Hong Kong SAR, China ; 2 School of Biomedical Sciences and Center of Novel Functional Molecules, 3 Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China ; 4 Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Yì-Xiáng J
authors.initials: YX
authors.lastname: Wáng
authors.affiliation: 1 Department of Chemistry, Institute of Creativity and Partner State Key Laboratory of Environmental and Biological Analysis, The Hong Kong Baptist University, Hong Kong SAR, China ; 2 School of Biomedical Sciences and Center of Novel Functional Molecules, 3 Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China ; 4 Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Christopher H K
authors.initials: CH
authors.lastname: Cheng
keywords: Deferoxamine (Def); gene delivery; imaging agents; nanoparticles (NPs); organic-inorganic hybrid composites