Abstract
Plasmid DNA was mixed with polyethyleneimine (PEI) and hyaluronic acid (HA) to afford ternary complexes with negative surface charge regardless of the mixing order. They showed reduced non-specific interactions with blood components. When DNA and PEI were mixed at a high concentration such as that used in in vivo experiments, they soon aggregated, and large particles were formed. On the other hand, pre-addition of HA to DNA prior to PEI effectively diminished the aggregation, and 10% (in volume) of the complexes remained as small particles with a diameter below 80 nm. Those negatively charged small ternary complexes induced a much stronger extra-gene expression in tumor than binary DNA/PEI complex after intratumoral or intravenous injection into the mice bearing B16 cells.
Abbreviations | ||
DAPI | = | 4′,6-diamidino-2-phenyl indole |
DMSO | = | dimethyl sulfoxide |
EMEM | = | Eagle's minimum essential medium |
FITC | = | fluorescein isothiocyanate isomer-I |
FBS | = | fetal bovine serum |
GFP | = | green fluorescent protein |
HA | = | hyaluronic acid |
ME | = | mercaptoethanol |
PEG-C | = | PEG derivative, having carboxylic acid side chain |
PEI | = | polyethyleneimine |
TR-HA | = | Texas Red-labeled HA |
TBA-HA | = | HA tetrabutylammonium salt |
Abbreviations | ||
DAPI | = | 4′,6-diamidino-2-phenyl indole |
DMSO | = | dimethyl sulfoxide |
EMEM | = | Eagle's minimum essential medium |
FITC | = | fluorescein isothiocyanate isomer-I |
FBS | = | fetal bovine serum |
GFP | = | green fluorescent protein |
HA | = | hyaluronic acid |
ME | = | mercaptoethanol |
PEG-C | = | PEG derivative, having carboxylic acid side chain |
PEI | = | polyethyleneimine |
TR-HA | = | Texas Red-labeled HA |
TBA-HA | = | HA tetrabutylammonium salt |