Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Biomed Mater Res A. 2011 Feb;96(2):456-65. doi: 10.1002/jbm.a.32994. Epub 2010 Dec 9.

Enzyme-synthesized poly(amine-co-esters) as nonviral vectors for gene delivery.

Author information

  • 1School of Life Science and Technology, Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.

Abstract

A family of biodegradable poly(amine-co-esters) was synthesized in one step via enzymatic copolymerization of diesters with amino-substituted diols. Diesters of length C(4) -C(12) (i.e., from succinate to dodecanedioate) were successfully copolymerized with diethanolamines with either an alkyl (methyl, ethyl, n-butyl, t-butyl) or an aryl (phenyl) substituent on the nitrogen. Upon protonation at slightly acidic conditions, these poly(amine-co-esters) readily turned to cationic polyelectrolytes, which were capable of condensing with polyanionic DNA to form nanometer-sized polyplexes. In vitro screening with pLucDNA revealed that two of the copolymers, poly(N-methyldiethyleneamine sebacate) (PMSC) and poly(N-ethyldiethyleneamine sebacate) (PESC), possessed comparable or higher transfection efficiencies compared with Lipofectamine 2000. PMSC/pLucDNA and PESC/pLucDNA nanoparticles had desirable particle sizes (40-70 nm) for cellular uptake and were capable of functioning as proton sponges to facilitate endosomal escape after cellular uptake. These polyplex nanoparticles exhibited extremely low cytotoxicity. Furthermore, in vivo gene transfection experiments revealed that PMSC is a substantially more effective gene carrier than PEI in delivering pLucDNA to cells in tumors in mice. All these properties suggest that poly(amine-co-esters) are promising nonviral vectors for safe and efficient DNA delivery in gene therapy.

2010 Wiley Periodicals, Inc.

PMID:
21171165
[PubMed - indexed for MEDLINE]
PMCID:
PMC3080021
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for John Wiley & Sons, Inc. Icon for PubMed Central
    Loading ...
    Write to the Help Desk