Enhancement of star vector-based gene delivery to endothelial cells by addition of RGD-peptide.
This study aimed to investigate the feasibility of using a cationic nonviral gene carrier in endothelial cells for enhancing gene expression by the addition of an integrin-binding RGD peptide. A 4-branched cationic polymer of poly( N,N-dimethylaminopropylacrylamide) (star vector), developed as a gene carrier, could complex with the luciferase-encoding plasmid DNA under a charge ratio of 5 (vector/pDNA) to form polymer/DNA complexes (polyplexes). The addition of the RGD-containing peptide (GRGDNP) to the polyplex solution led to a decrease in the zeta-potential from ca. +30 to +20 mV along with the reduction in the particle size from ca. 300 to 200 nm. Additionally, a marked inhibition of polyplex aggregation was observed, indicating the coating of the polyplex surface with RGD peptides. A transfection study on endothelial cells showed that the luciferase activity increased with the amount of RGD peptides added to the polyplexes and exhibited minimal cellular cytotoxicity. The transfection activity further increased when cyclic RGD peptides (RGDFV) were used; the activity with RGD peptide addition was approximately 8-fold compared to that without RGD peptide addition. Gene delivery to endothelial cells was significantly enhanced by only the addition of RGD peptides to star vector-based polyplexes.
Ishikawa
Ayaka
A
Department of Bioengineering, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, Osaka, Japan.
Zhou
Yue-Min
YM
Kambe
Nobuaki
N
Nakayama
Yasuhide
Y
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004727:Endothelium / Q000166:cytology*; D005822:Genetic Vectors; D009842:Oligopeptides / Q000008:administration & dosage*
D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid