Journal
JOURNAL OF CONTROLLED RELEASE
Volume 155, Issue 1, Pages 77-87Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2010.10.006
Keywords
Nonviral vectors; Dendrimers; Biocompatibility; In vivo; Gene delivery
Funding
- National Basic Research Program of China (National 973 program) [2005CB623903]
- National Natural Science Foundation of China [50633020, 50603015]
Ask authors/readers for more resources
We report the synthesis and characterization of different generations of dendritic poly(L-lysine) vectors, and their use for in vivo gene transfection. Gel retardation assay revealed that the dendrimers could form complexes with plasmid DNAs (pDNAs), evident from the inhibition of the migration of pDNA at the N/P ratios of 0.5, 1 and 2 by G3, G4 and G5 dendritic generations, respectively. DNase I assay revealed the protection of pDNA acquired from the complexation with dendrimers from nuclease-catalyzed degradation, with the protection capacity of G5 being even stronger than poly(ethyleneimine) (PEI). Atomic force microscopy (AFM) revealed that all 4 generations of dendrimer/DNA complexes studied were of similar particle sizes within 100-200 nm. Zeta potential measurements showed that as the N/P ratio increased from 1 to 25, all dendrimer/pDNA complexes gradually changed from negative to positive charges. The higher generations tended to produce the greater positive potentials, indicating a stronger potency of the complexes to interact with negatively charged cell membranes. In vitro and in vivo cytotoxicity evaluations showed good biocompatibility of the dendrimers and their complexes over the different N/P ratios studied. In vitro gene transfection revealed higher efficiency of G5 than other dendrimers and insensitive variation to the presence of serum. Given its similar transfection efficiency to PEI but lower toxicity to cultured cells, dendrimer G5 could be a better candidate for gene delivery. (C) 2010 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available