Galactosylated poly(2-(2-aminoethyoxy)ethoxy)phosphazene/DNA complex nanoparticles: in vitro and in vivo evaluation for gene delivery.

Abstract

To achieve efficient gene delivery to the tumor after intravenous administration, biodegradable poly(2-(2-aminoethyoxy)ethoxy)phosphazene (PAEP) was modified by lactobionic acid, bearing a galactose group as a targeting ligand. Galactosylated poly(2-(2-aminoethyoxy)ethoxy)phosphazene (Gal-PAEP) with 4.9% substitution degree of galactose could condense pDNA into nanoparticles with a size around 130 nm at the polymer/DNA ratio (N/P) of 2-40. For BEL-7402 cells, the in vitro transfection efficiency of gal-PAEP/DNA complex nanoparticles (gal-PACNs) was much higher than that of the PAEP/DNA complex nanoparticles (PACNs). MTT assay indicated that the cytotoxicity of PACNs significantly decreased after conjugating with the galactose moiety. Gal-PACNs displayed the selective gene expression in the tumor and liver with relatively low gene expression in the lung or other organs compared with PACNs. These results suggested that gal-PACNs could be a promising targeting gene carrier to deliver a therapeutic gene in future.

• Authors: Yongxin Yang, Zhiwen Zhang, Lingli Chen, Wangwen Gu, Yaping Li
• Journal: Biomacromolecules (Biomacromolecules) Vol. 11 Issue 4 Pg. 927-33 (Apr 12 2010) ISSN: 1526-4602 [Electronic] United States
• PMID: 20302354 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aziridines
• Organophosphorus Compounds
• phosphazine
• DNA
• Galactose

Topics

• Animals
• Aziridines (chemistry)
• COS Cells
• Carcinoma, Hepatocellular (drug therapy, genetics)
• Cell Proliferation
• Chlorocebus aethiops
• DNA (chemistry, metabolism)
• Galactose (chemistry)
• Gene Targeting
• Gene Transfer Techniques
• HeLa Cells
• Humans
• In Vitro Techniques
• Liver Neoplasms, Experimental (drug therapy, genetics)
• Male
• Mice
• Mice, Inbred BALB C
• Nanoparticles
• Organophosphorus Compounds (chemistry, pharmacology)
• Xenograft Model Antitumor Assays