title: Redox-Sensitive Polymer/SPIO Nanocomplexes for Efficient Magnetofection and MR Imaging of Human Cancer Cells.
abstract: Magnetofection has received increasing attention for its great potential on gene therapy. To promote its clinical therapeutic applications, development of safe and effective magnetic nanocarriers is in high demand. Herein, we present a redox-sensitive polymer/metal nanocomplex system (PSPIO) for efficient magnetofection and magnet resonance imaging (MRI) on cancer cells. PSPIO was prepared by modifying SPIO with redox-sensitive polyethylenimine (SSPEI) via a ligand exchange process. PSPIO could efficiently condense plasmid DNA (pDNA) into nanoparticles, which exhibited several favorable properties for gene delivery, including protection of nucleic acids from enzymatic degradation, stable colloids in serum, and redox-responsive pDNA release. As a potential MR imaging agent, PSPIO displayed good magnetization (28.3 emu/g) and dose-dependent T2-weighted imaging contrast (R2 = 291.1 s(-1) mM(-1)) in vitro. The use of redox-sensitive SSPEI polymer contributed to much lower cytotoxicity of PSPIO compared to nondegradable bPEI25k. In vitro transfection efficiency of PSPIO was significantly enhanced under an external magnetic field. In the presence of serum, PSPIO exhibited higher transgene expression than SSPEI or bPEI25k polymer on mouse glioma (ALTS1C1) or human prostate cancer (PC3) cell lines. Taken together, it is demonstrated that PSPIO possess great potential for cancer gene therapy and molecular imaging.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, 30013, Taiwan.
authors.forename: Rih-Yang
authors.initials: RY
authors.lastname: Huang
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, 30013, Taiwan.
authors.forename: Pin-Hsin
authors.initials: PH
authors.lastname: Chiang
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, 30013, Taiwan.
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Hsiao
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, 30013, Taiwan.
authors.forename: Chun-Chiao
authors.initials: CC
authors.lastname: Chuang
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, 30013, Taiwan.
authors.forename: Chien-Wen
authors.initials: CW
authors.lastname: Chang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006801:Humans; D060526:Magnetic Fields; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011094:Polyethyleneimine / Q000737:chemistry*; D019076:Transgenes
chemical_list: D011094:Polyethyleneimine