TY - JOUR
T1 - Stabilizing of plasmid DNA in vivo by PEG-modified cationic gold nanoparticles and the gene expression assisted with electrical pulses
AU - Kawano, Takahito
AU - Yamagata, Masato
AU - Takahashi, Hironobu
AU - Niidome, Yasuro
AU - Yamada, Sunao
AU - Katayama, Yoshiki
AU - Niidome, Takuro
N1 - Funding Information:
This research was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 16023251) and the Japan Society for the Promotion of Science (No. 16790106).
PY - 2006/4/10
Y1 - 2006/4/10
N2 - This study aimed to investigate the benefits of combining the use of PEG-modified cationic gold nanoparticles with electroporation for in vivo gene delivery. PEG-modified cationic gold nanoparticles were prepared by NaBH 4 reduction of HAuCl4 in the presence of 2-aminoethanethiol and mPEG-SH. Zeta-potential of the particles was nearly neutral (+ 0.1 mV). After forming complexes with plasmid DNA at a w/w ratio of 8.4, nanoparticle complexes were 90 nm for at least 60 min and showed a negative zeta-potential. After intravenous injection of DNA-nanoparticle complexes, 20% of gold were detected in blood at 120 min after injection and 5% of DNA were observed in blood after 5 min, suggesting that PEG-modified nanoparticles were stably circulating in the blood flow, but some of the DNA bound to particles degraded during circulation. When electroporation was applied to a lobe of the liver following injection of DNA-nanoparticle complexes, significant gene expression was specifically observed in the pulsed lobe. We concluded that PEG-modified nanoparticles maintained DNA more stably in the blood flow than in the case of naked DNA and electroporation assisted in restricted gene expression of circulating DNA in limited areas of the liver.
AB - This study aimed to investigate the benefits of combining the use of PEG-modified cationic gold nanoparticles with electroporation for in vivo gene delivery. PEG-modified cationic gold nanoparticles were prepared by NaBH 4 reduction of HAuCl4 in the presence of 2-aminoethanethiol and mPEG-SH. Zeta-potential of the particles was nearly neutral (+ 0.1 mV). After forming complexes with plasmid DNA at a w/w ratio of 8.4, nanoparticle complexes were 90 nm for at least 60 min and showed a negative zeta-potential. After intravenous injection of DNA-nanoparticle complexes, 20% of gold were detected in blood at 120 min after injection and 5% of DNA were observed in blood after 5 min, suggesting that PEG-modified nanoparticles were stably circulating in the blood flow, but some of the DNA bound to particles degraded during circulation. When electroporation was applied to a lobe of the liver following injection of DNA-nanoparticle complexes, significant gene expression was specifically observed in the pulsed lobe. We concluded that PEG-modified nanoparticles maintained DNA more stably in the blood flow than in the case of naked DNA and electroporation assisted in restricted gene expression of circulating DNA in limited areas of the liver.
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U2 - 10.1016/j.jconrel.2005.12.022
DO - 10.1016/j.jconrel.2005.12.022
M3 - Article
C2 - 16487614
AN - SCOPUS:33645223448
SN - 0168-3659
VL - 111
SP - 382
EP - 389
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 3
ER -