A Comparative Evaluation of Disulfide-Linked and Hydrophobically-Modified PEI for Plasmid Delivery

被引:25
作者
Bahadur, Remant K. C. [1 ]
Uludag, Hasan [1 ,2 ,3 ]
机构
[1] Univ Alberta, Dept Chem & Mat Engn, Fac Engn, Edmonton, AB T6G 2G6, Canada
[2] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2G6, Canada
[3] Univ Alberta, Dept Biomed Engn, Fac Med & Dent, Edmonton, AB T6G 2G6, Canada
关键词
Gene therapy; non-viral vector; poly(ethylene imine); disulfide-linkage; hydrophobic modification; BIOREDUCIBLE POLY(AMIDO AMINE)S; NONVIRAL GENE DELIVERY; POLYMERIC VESICLES; NUCLEIC-ACIDS; VECTORS; DNA; POLYETHYLENIMINES; COMPLEXES; DESIGN;
D O I
10.1163/092050610X496297
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Non-viral gene therapy has become an important approach for treatment of hereditary and acquired diseases as a result of better understanding of molecular mechanisms involved in disease development. To design more effective gene carriers, plasmid DNA (pDNA) delivery to 293T cells was investigated by using two types of polymeric carriers; polymer constructed with disulfide (-S-S-) linkages and polymers modified with hydrophobic moieties. The base polymer used for this study was 2-kDa poly(ethylene imine) (PEI2), a relatively cell-compatible but ineffective gene carrier. The -S-S-linking was achieved via Michael addition reaction using cystamine bisacrylamide (CBA), whereas hydrophobic modification by N-acylation of PEI2 amines with palmitoyl chloride (PA). The cytotoxicity of the polymers was found to be lower than that of the 25-kDa branched PEI, but both types of modifications increased the toxicity of PEI2 to some extent. The polymers were able to form polyplexes with pDNA with variable hydrodynamic sizes (130-600 nm) and zeta-potential (3.6-20.9 mV). Based on the expression of the reporter gene Enhanced Green Fluorescent Protein (EGFP), disulfide linking significantly increased the efficiency of native PEI2, which was not effective on its own. The PA-modified PEI2 was also effective for gene delivery, but disulfide linkage of this polymer did not increase its efficiency any further. Our results showed that hydrophobic modification of 2-kDa PEI significantly improved its transfection efficiency but improvements in transfection efficiency as a result of disulfide linking was dependent on the nature of the polymeric building blocks. (C) Koninklijke Brill NV, Leiden, 2011
引用
收藏
页码:873 / 892
页数:20
相关论文
共 25 条
[1]   Palmitic acid-modified poly-L-lysine for non-viral delivery of plasmid DNA to skin fibroblasts [J].
Abbasi, Meysam ;
Uludag, Hasan ;
Incani, Vanessa ;
Olson, Cori ;
Lin, Xiaoyue ;
Clements, Basak Acan ;
Rutkowski, Dorothy ;
Ghahary, Aziz ;
Weinfeld, Michael .
BIOMACROMOLECULES, 2007, 8 (04) :1059-1063
[2]   Direct real-time molecular scale visualisation of the degradation of condensed DNA complexes exposed to DNase I [J].
Abdelhady, HG ;
Allen, S ;
Davies, MC ;
Roberts, CJ ;
Tendler, SJB ;
Williams, PM .
NUCLEIC ACIDS RESEARCH, 2003, 31 (14) :4001-4005
[3]   Delivery of Nucleic Acids via Disulfide-Based Carrier Systems [J].
Bauhuber, Sonja ;
Hozsa, Constantin ;
Breunig, Miriam ;
Goepferich, Achim .
ADVANCED MATERIALS, 2009, 21 (32-33) :3286-3306
[4]   Gene delivery with tow molecular weight linear polyethytenimines [J].
Breunig, M ;
Lungwitz, U ;
Liebl, R ;
Fontanari, C ;
Klar, J ;
Kurtz, A ;
Blunk, T ;
Goepferich, A .
JOURNAL OF GENE MEDICINE, 2005, 7 (10) :1287-1298
[5]   Breaking up the correlation between efficacy and toxicity for nonviral gene delivery [J].
Breunig, Miriam ;
Lungwitz, Uta ;
Liebl, Renate ;
Goepferich, Achim .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (36) :14454-14459
[6]   Preliminary characterization of novel amino acid based polymeric vesicles as gene and drug delivery agents [J].
Brown, MD ;
Schätzlein, A ;
Brownlie, A ;
Jack, V ;
Wang, W ;
Tetley, L ;
Gray, AI ;
Uchegbu, IF .
BIOCONJUGATE CHEMISTRY, 2000, 11 (06) :880-891
[7]   Reducible poly(amido ethylenimine)s designed for triggered intracellular gene delivery [J].
Christensen, Lane V. ;
Chang, Chien-Wen ;
Kim, Won Jong ;
Kim, Sung Wan ;
Zhong, Zhiyuan ;
Lin, Chao ;
Engbersen, Johan F. J. ;
Feijen, Jan .
BIOCONJUGATE CHEMISTRY, 2006, 17 (05) :1233-1240
[8]   New poly(amidoamine)s containing disulfide linkages in their main chain [J].
Emilitri, E ;
Ranucci, E ;
Ferruti, P .
JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY, 2005, 43 (07) :1404-1416
[9]   Efficient gene transfer using reversibly cross-linked low molecular weight polyethylenimine [J].
Gosselin, MA ;
Guo, WJ ;
Lee, RJ .
BIOCONJUGATE CHEMISTRY, 2001, 12 (06) :989-994
[10]   Uptake pathways and subsequent intracellular trafficking in nonviral gene delivery [J].
Khalil, IA ;
Kogure, K ;
Akita, H ;
Harashima, H .
PHARMACOLOGICAL REVIEWS, 2006, 58 (01) :32-45