Poly(ethylene glycol)-conjugated PAMAM dendrimer for biocompatible, high-efficiency DNA delivery

被引：373

作者：

Luo, D ^{[1
]}

Haverstick, K ^{[1
]}

Belcheva, N ^{[1
]}

Han, E ^{[1
]}

Saltzman, WM ^{[1
]}

机构：

[1] Cornell Univ, Sch Chem Engn, Ithaca, NY 14850 USA

来源：

MACROMOLECULES | 2002年 / 35卷 / 09期

关键词：

D O I：

10.1021/ma0106346

中图分类号：

O63 [高分子化学（高聚物）];

学科分类号：

070305 ; 080501 ; 081704 ;

摘要：

We demonstrate a simple and successful synthetic approach to devise a highly efficient DNA delivery system with low cytotoxicity and low cost. Polyamidoamine (PAMAM) dendrimer is a highly efficient DNA delivery agent, when compared to other chemical transfection reagents. Partially degraded, high-generation dendrimers offer even higher efficiency, presumably due to enhanced flexibility of the otherwise rigid dendrimer chains.' We hypothesized that chemical modification of low generation dendrimer with biocompatible poly(ethylene glycol) (PEG) chains would create a conjugate of PAMAM core with flexible PEG chains, which mimics the fractured high-generation dendrimer and produces high transfection efficiency. Generation 5 PAMAM was modified with 3400 molecular weight PEG. The novel conjugate produced a 20-fold increase in transfection efficiency compared with partially degraded dendrimer controls. The cytotoxicity of PEGylated dendrimers was very low. This extremely efficient, highly biocompatible, low-cost DNA delivery system can be readily used in basic research laboratories and may find future clinical applications.

引用

收藏

页码：3456 / 3462

页数：7

相关论文

共 21 条

[1] Synthesis and characterization of polymer-(multi)-peptide conjugates for control of specific cell aggregation [J].

Belcheva, N ;

Baldwin, SP ;

Saltzman, WM .

JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION, 1998, 9 (03) :207-226

[2] Synthesis and biological activity of polyethylene glycol-mouse nerve growth factor conjugate [J].

Belcheva, N ;

Woodrow-Mumford, K ;

Mahoney, MJ ;

Saltzman, WM .

BIOCONJUGATE CHEMISTRY, 1999, 10 (06) :932-937

[3] DNA complexing with polyamidoamine dendrimers: Implications for transfection [J].

Bielinska, AU ;

Chen, CL ;

Johnson, J ;

Baker, JR .

BIOCONJUGATE CHEMISTRY, 1999, 10 (05) :843-850

[4] A VERSATILE VECTOR FOR GENE AND OLIGONUCLEOTIDE TRANSFER INTO CELLS IN CULTURE AND IN-VIVO - POLYETHYLENIMINE [J].

BOUSSIF, O ;

LEZOUALCH, F ;

ZANTA, MA ;

MERGNY, MD ;

SCHERMAN, D ;

DEMENEIX, B ;

BEHR, JP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (16) :7297-7301

[5] 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

[6] 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

[7] 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

[8] Sensing a self-assembled protein structure through its permeation by a ferrocene labeled poly(ethylene glycol) chain [J].

Demaille, C ;

Moiroux, J .

JOURNAL OF PHYSICAL CHEMISTRY B, 1999, 103 (45) :9903-9909

[9] POLYAMIDOAMINE CASCADE POLYMERS MEDIATE EFFICIENT TRANSFECTION OF CELLS IN CULTURE [J].

HAENSLER, J ;

SZOKA, FC .

BIOCONJUGATE CHEMISTRY, 1993, 4 (05) :372-379

[10] PREPARATION OF POLYMERS WITH CONTROLLED MOLECULAR ARCHITECTURE - A NEW CONVERGENT APPROACH TO DENDRITIC MACROMOLECULES [J].

HAWKER, CJ ;

FRECHET, JMJ .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1990, 112 (21) :7638-7647