Abstract
In regard to gene vectors for cancer gene therapy, their percolation into the tumor tissue should be essential for successful outcome. Here, we studied the tumor penetrability of nonviral vectors (polyplexes) after incubation with the multicellular tumor spheroid (MCTS) models and intratumoral (i.t.) injection into subcutaneous tumors. As a result, polyethylene glycolated (PEGylated), core-shell type polyplexes (polyplex micelles) showed facilitated percolation and improved transfection inside the tumor tissue, whereas conventional polyplexes from cationic polymers exhibited limited percolation and localized transfection. Furthermore, the transfection of hypoxia-responsive plasmid demonstrated that polyplex micelles allowed the transfection to the hypoxic region of the tumor tissue in both in vitro and in vivo experiments. To the best of our knowledge, our results demonstrated for the first time that polyplex micelles might show improved tumor penetrability over cationic polyplexes, thereby achieving transfection into the inside of the tumor tissue.
| Original language | English |
|---|---|
| Pages (from-to) | 1404-1410 |
| Number of pages | 7 |
| Journal | Molecular Therapy |
| Volume | 17 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2009 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Molecular Medicine
- Genetics
- Drug Discovery
- Pharmacology
Cite this
Enhanced percolation and gene expression in tumor hypoxia by PEGylated polyplex micelles. / Han, Muri; Oba, Makoto; Nishiyama, Nobuhiro; Kano, Mitsunobu; Kizaka-Kondoh, Shinae; Kataoka, Kazunori.
In: Molecular Therapy, Vol. 17, No. 8, 2009, p. 1404-1410.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Enhanced percolation and gene expression in tumor hypoxia by PEGylated polyplex micelles
AU - Han, Muri
AU - Oba, Makoto
AU - Nishiyama, Nobuhiro
AU - Kano, Mitsunobu
AU - Kizaka-Kondoh, Shinae
AU - Kataoka, Kazunori
PY - 2009
Y1 - 2009
N2 - In regard to gene vectors for cancer gene therapy, their percolation into the tumor tissue should be essential for successful outcome. Here, we studied the tumor penetrability of nonviral vectors (polyplexes) after incubation with the multicellular tumor spheroid (MCTS) models and intratumoral (i.t.) injection into subcutaneous tumors. As a result, polyethylene glycolated (PEGylated), core-shell type polyplexes (polyplex micelles) showed facilitated percolation and improved transfection inside the tumor tissue, whereas conventional polyplexes from cationic polymers exhibited limited percolation and localized transfection. Furthermore, the transfection of hypoxia-responsive plasmid demonstrated that polyplex micelles allowed the transfection to the hypoxic region of the tumor tissue in both in vitro and in vivo experiments. To the best of our knowledge, our results demonstrated for the first time that polyplex micelles might show improved tumor penetrability over cationic polyplexes, thereby achieving transfection into the inside of the tumor tissue.
AB - In regard to gene vectors for cancer gene therapy, their percolation into the tumor tissue should be essential for successful outcome. Here, we studied the tumor penetrability of nonviral vectors (polyplexes) after incubation with the multicellular tumor spheroid (MCTS) models and intratumoral (i.t.) injection into subcutaneous tumors. As a result, polyethylene glycolated (PEGylated), core-shell type polyplexes (polyplex micelles) showed facilitated percolation and improved transfection inside the tumor tissue, whereas conventional polyplexes from cationic polymers exhibited limited percolation and localized transfection. Furthermore, the transfection of hypoxia-responsive plasmid demonstrated that polyplex micelles allowed the transfection to the hypoxic region of the tumor tissue in both in vitro and in vivo experiments. To the best of our knowledge, our results demonstrated for the first time that polyplex micelles might show improved tumor penetrability over cationic polyplexes, thereby achieving transfection into the inside of the tumor tissue.
UR - http://www.scopus.com/inward/record.url?scp=68249112400&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=68249112400&partnerID=8YFLogxK
U2 - 10.1038/mt.2009.119
DO - 10.1038/mt.2009.119
M3 - Article
C2 - 19471245
AN - SCOPUS:68249112400
VL - 17
SP - 1404
EP - 1410
JO - Molecular Therapy
JF - Molecular Therapy
SN - 1525-0016
IS - 8
ER -