title: MR traceable delivery of p53 tumor suppressor gene by PEI-functionalized superparamagnetic iron oxide nanoparticles.
abstract: Cancer gene therapy involves the replacement of missing or altered genes with healthy ones. In this paper, we have proposed tumor suppressor gene-carrying superparamagnetic iron oxide nanoparticles (SPIONs) for anti-cancer gene therapy. Thermally crosslinked SPIONs (TCL-SPIONs) were conjugated with branched polyethylenimine (PEI 1800 Da) by EDC-NHS chemistry for p53 plasmid DNA delivery. The morphology of the bPEI conjugated TCL-SPIONs (bPEI-TCL-SPION) and pDNA-loaded bPEI-TCL-SPION nanoparticles was measured using transmission electron microscopy (TEM). The particle sizes of the pDNA-loaded bPEI-TCL-SPION nanoparticles were also confirmed by dynamic light scattering, and ranged from 100 to 130 nm, depending on the molar charge ratio. The fluorescently labeled pDNA was complexed with bPEI-TCL-SPION and its intracellular internalization was investigated using confocal microscopy. The p53 plasmid-loaded bPEI-TCL-SPION nanoparticles achieved significantly higher p53 tumor suppressor gene expression and cellular viability compared to positive controls. The expressed wild-type p53 protein suppressed tumor cell proliferation as compared to the mutant control. When transgene expression of the p53 tumor suppressor gene was evaluated at the mRNA level and quantified using real-time PCR, the results were highly dependent on the molar charge ratio (N/P) as well as the cancer cell type. SPIONs internalized within cancer cells were tracked by magnetic resonance (MR) imaging. It was concluded that bPEI-TCL-SPION could be used as efficient gene delivery carriers that can be tracked by MR imaging.
authors: Department of Biomedical Sciences, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-746, South Korea.
authors: H J
authors: HJ
authors: Lee
authors: Y T C
authors: YT
authors: Nguyen
authors: M
authors: M
authors: Muthiah
authors: H
authors: H
authors: Vu-Quang
authors: R
authors: R
authors: Namgung
authors: W J
authors: WJ
authors: Kim
authors: M K
authors: MK
authors: Yu
authors: S
authors: S
authors: Jon
authors: I K
authors: IK
authors: Lee
authors: Y Y
authors: YY
authors: Jeong
authors: I K
authors: IK
authors: Park
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D003911:Dextrans; D020869:Gene Expression Profiling / Q000379:methods; D016153:Genes, Suppressor; D006801:Humans; D007097:Imines / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics*; D011095:Polyethylenes / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D003287:Contrast Media; D003911:Dextrans; D007097:Imines; D058185:Magnetite Nanoparticles; D053769:Nanocapsules; D011095:Polyethylenes; D016159:Tumor Suppressor Protein p53; C097921:ferumoxtran-10; C505405:poly(ethylene imine)