PAMAM-PEG-PAMAM: Novel triblock copolymer as a biocompatible and efficient gene delivery carrier

被引:181
作者
Kim, T
Seo, HJ
Choi, JS
Jang, HS
Baek, J
Kim, K
Park, JS
机构
[1] Seoul Natl Univ, Sch Chem & Mol Engn, Seoul 151742, South Korea
[2] Chungnam Natl Univ, Dept Biochem, Taejon 305764, South Korea
关键词
D O I
10.1021/bm049563j
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A novel triblock copolymer, PAMAM-block-PEG-block-PAMAM was synthesized and applied as a gene carrier. PAMAM dendrimer is proven to be an efficient gene carrier itself, but it is associated with certain problems such as low water solubility and considerable cytotoxicity. Therefore, we introduced PEG to engineer a nontoxic and highly transfection efficient polymeric gene carrier because PEG is known to convey water-solubility and biocompatibility to the conjugated copolymer. This copolymer could achieve self-assembly with plasmid DNA, forming compact nanosized particles with a narrow size distribution. Fulfilling our expectations, the copolymer was found to form highly water-soluble polyplexes with plasmid DNA, showed little cytotoxicity despite its poor degradability, and finally achieved high transfection efficiency comparable to PEI in 293 cells. Consequently, these data show that an approach involving the introduction of PEG to create a tree-like cationic copolymer possesses a great potential for use in gene delivery systems.
引用
收藏
页码:2487 / 2492
页数:6
相关论文
共 24 条
[1]   DNA complexing with polyamidoamine dendrimers: Implications for transfection [J].
Bielinska, AU ;
Chen, CL ;
Johnson, J ;
Baker, JR .
BIOCONJUGATE CHEMISTRY, 1999, 10 (05) :843-850
[2]   Synthesis of a barbell-like triblock copolymer, poly(L-lysine) dendrimer-block-poly(ethylene glycol)-block-poly(L-lysine) dendrimer, and its self-assembly with plasmid DNA [J].
Choi, JS ;
Joo, DK ;
Kim, CH ;
Kim, K ;
Park, JS .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (03) :474-480
[3]   Poly(ethylene glycol)-block-poly(L-lysine) dendrimer:: Novel linear polymer/dendrimer block copolymer forming a spherical water-soluble polyionic complex with DNA [J].
Choi, JS ;
Lee, EJ ;
Choi, YH ;
Jeong, YJ ;
Park, JS .
BIOCONJUGATE CHEMISTRY, 1999, 10 (01) :62-65
[4]   Lactose-poly(ethylene glycol)-grafted poly-L-lysine as hepatoma cell-targeted gene carrier [J].
Choi, YH ;
Liu, F ;
Park, JS ;
Kim, SW .
BIOCONJUGATE CHEMISTRY, 1998, 9 (06) :708-718
[5]   Cationic polymer based gene delivery systems [J].
De Smedt, SC ;
Demeester, J ;
Hennink, WE .
PHARMACEUTICAL RESEARCH, 2000, 17 (02) :113-126
[6]  
Eichman, 2000, Pharm Sci Technol Today, V3, P232, DOI 10.1016/S1461-5347(00)00273-X
[7]   Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications [J].
Esfand, R ;
Tomalia, DA .
DRUG DISCOVERY TODAY, 2001, 6 (08) :427-436
[8]   RE-EXAMINATION AND FURTHER DEVELOPMENT OF A PRECISE AND RAPID DYE METHOD FOR MEASURING CELL-GROWTH CELL KILL [J].
HANSEN, MB ;
NIELSEN, SE ;
BERG, K .
JOURNAL OF IMMUNOLOGICAL METHODS, 1989, 119 (02) :203-210
[9]   Synthesis and solution properties of new linear-dendritic diblock copolymers [J].
Iyer, J ;
Fleming, K ;
Hammond, PT .
MACROMOLECULES, 1998, 31 (25) :8757-8765
[10]   The influence of surface modification on the cytotoxicity of PAMAM dendrimers [J].
Jevprasesphant, R ;
Penny, J ;
Jalal, R ;
Attwood, D ;
McKeown, NB ;
D'Emanuele, A .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2003, 252 (1-2) :263-266