title: A general strategy to achieve ultra-high gene transfection efficiency using lipid-nanoparticle composites.
abstract: Gene therapy provides a new hope for previously "incurable" diseases. Low gene transfection efficiency, however, is the bottle-neck to the success of gene therapy. It is very challenging to develop non-viral nanocarriers to achieve ultra-high gene transfection efficiencies. Herein, we report a novel design of "tight binding-but-detachable" lipid-nanoparticle composite to achieve ultrahigh gene transfection efficiencies of 60∼82%, approaching the best value (∼90%) obtained using viral vectors. We show that Fe@CNPs nanoparticles coated with LP-2000 lipid molecules can be used as gene carriers to achieve ultra-high (60-80%) gene transfection efficiencies in HeLa, U-87MG, and TRAMP-C1 cells. In contrast, Fe@CNPs having surface-covalently bound N,N,N-trimethyl-N-2-methacryloxyethyl ammonium chloride (TMAEA) oligomers can only achieve low (23-28%) gene transfection efficiencies. Similarly ultrahigh gene transfection/expression was also observed in zebrafish model using lipid-coated Fe@CNPs as gene carriers. Evidences for tight binding and detachability of DNA from lipid-nanoparticle nanocarriers will be presented.
authors: Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors: Raviraj
authors: R
authors: Vankayala
authors: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors: Chi-Shiun
authors: CS
authors: Chiang
authors: Department of Biological Science, National Chiao Tung University, Hsinchu 30013, Taiwan.
authors: Jui-I
authors: JI
authors: Chao
authors: Department of Biological Science, National Chiao Tung University, Hsinchu 30013, Taiwan.
authors: Chiun-Jye
authors: CJ
authors: Yuan
authors: Department of Biological Science, National Chiao Tung University, Hsinchu 30013, Taiwan; Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan; Department of Obstetrics and Gynecology, Department of Medical Research, Stem Cell Lab, Mackay Memorial Hospital, Taipei 10449, Taiwan.
authors: Shyr-Yeu
authors: SY
authors: Lin
authors: Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan. Electronic address: kchwang@mx.nthu.edu.tw.
authors: Kuo Chu
authors: KC
authors: Hwang
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002470:Cell Survival; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry; D005492:Folic Acid / Q000737:chemistry; D015316:Genetic Therapy / Q000379:methods; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007501:Iron / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry; D008689:Methacrylates / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D037742:Nanotubes, Carbon / Q000737:chemistry; D013499:Surface Properties; D014162:Transfection / Q000379:methods*; D015027:Zebrafish
chemical_list: C120889:2-(trimethylammonio)ethyl methacrylate; D008055:Lipids; D008689:Methacrylates; D037742:Nanotubes, Carbon; D049452:Green Fluorescent Proteins; D000255:Adenosine Triphosphate; D004247:DNA; D005492:Folic Acid; D007501:Iron
keywords: Carbon nanoparticles; Cytotoxicity; Gene therapy; Gene transfection; Nanocarriers; Zebrafish