title: Cationic lipid-nanoceria hybrids, a novel nonviral vector-mediated gene delivery into mammalian cells: investigation of the cellular uptake mechanism.
abstract: Gene therapy is a promising technique for the treatment of various diseases. The development of minimally toxic and highly efficient non-viral gene delivery vectors is the most challenging undertaking in the field of gene therapy. Here, we developed dimethyldioctadecylammonium bromide (DODAB)-nanoceria (CeO2) hybrids as a new class of non-viral gene delivery vectors. These DODAB-modified CeO2 nanoparticles (CeO2/DODAB) could effectively compact the pDNA, allowing for highly efficient gene transfection into the selected cell lines. The CeO2/DODAB nanovectors were also found to be non-toxic and did not induce ROS formation as well as any stress responsive and pro-survival signaling pathways. The overall vector performance of CeO2/DODAB nanohybrids was comparable with lipofectamine and DOTAP, and higher than calcium phosphate and DEAE-dextran for transfecting small plasmids. The increased cellular uptake of the nanovector/DNA complexes through clathrin- and caveolae-mediated endocytosis and subsequent release from the endosomes further support the increased gene transfection efficiency of the CeO2/DODAB vectors. Besides, CeO2/DODAB nanovectors could transfect genes in vivo without any sign of toxicity. Taken together, this new nano-vector has the potential to be used for gene delivery in biomedical applications.
authors.affiliation: Department of Stem Cell and Regenerative Biology, Humanized Pig Research Center (SRC), Konkuk University, Seoul 143-701, South Korea.
authors.forename: Joydeep
authors.initials: J
authors.lastname: Das
authors.affiliation: Department of Stem Cell and Regenerative Biology, Humanized Pig Research Center (SRC), Konkuk University, Seoul 143-701, South Korea.
authors.forename: Jae Woong
authors.initials: JW
authors.lastname: Han
authors.affiliation: Department of Stem Cell and Regenerative Biology, Humanized Pig Research Center (SRC), Konkuk University, Seoul 143-701, South Korea.
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Stem Cell and Regenerative Biology, Humanized Pig Research Center (SRC), Konkuk University, Seoul 143-701, South Korea.
authors.forename: Hyuk
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Stem Cell and Regenerative Biology, Humanized Pig Research Center (SRC), Konkuk University, Seoul 143-701, South Korea.
authors.forename: Ssang-Goo
authors.initials: SG
authors.lastname: Cho
authors.affiliation: Department of Stem Cell and Regenerative Biology, Humanized Pig Research Center (SRC), Konkuk University, Seoul 143-701, South Korea.
authors.forename: Chankyu
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Stem Cell and Regenerative Biology, Humanized Pig Research Center (SRC), Konkuk University, Seoul 143-701, South Korea.
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
authors.affiliation: Department of Stem Cell and Regenerative Biology, Humanized Pig Research Center (SRC), Konkuk University, Seoul 143-701, South Korea.
authors.forename: Jin-Hoi
authors.initials: JH
authors.lastname: Kim
mesh_terms: D002412:Cations; D045744:Cell Line, Tumor; D002563:Cerium / Q000737:chemistry*; D003637:DEAE-Dextran; D004247:DNA / Q000378:metabolism; D004705:Endocytosis; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D057446:Hydrodynamics; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010957:Plasmids / Q000378:metabolism; D000644:Quaternary Ammonium Compounds; D013052:Spectrometry, X-Ray Emission; D017550:Spectroscopy, Fourier Transform Infrared; D014162:Transfection
chemical_list: D002412:Cations; D008055:Lipids; C086724:Lipofectamine; D000644:Quaternary Ammonium Compounds; D049452:Green Fluorescent Proteins; C015831:dimethyldioctadecylammonium; D002563:Cerium; C030583:ceric oxide; D004247:DNA; D003637:DEAE-Dextran