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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Hyperthermia-induced targeting of thermosensitive gene carriers to tumors.
Hum. Gene Ther. 19, 1283-1292 (2008)
Locoregional hyperthermia (HT) can be used for site-directed activation of macromolecular drug delivery systems. We have developed a gene delivery system based on thermosensitive block copolymers (TSCs) with a phase transition temperature of 42 degrees C [Zintchenko, A., Ogris, M., and Wagner, E. (2006). Bioconjug. Chem. 17, 766-772], in which the statistical copolymer of vinylpyrrolidinone and N-isopropylacryamide is grafted on polyethylenimine (PEI). Here we applied polyplexes consisting of plasmid DNA and TSCs systemically in A/J mice bearing a syngeneic Neuro2A neuroblastoma tumor subcutaneously in each hind limb. One limb was selectively treated by HT at 42 degrees C, at the same time that polyplexes were injected via the tail vein. Hyperthermia led to increased accumulation of thermosensitive polymer and aggregation of thermosensitive polyplexes in HT-treated tumors, resulting in up to 10-fold increased DNA deposition compared with non-HT-treated tumor. The level of transgene expression induced by TSC polyplexes in HT-treated tumors was significantly higher and selective for tumor tissue. With nonthermosensitive PEI polyplexes HT did not influence transgene deposition or expression in tumor.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
in-vivo; local hyperthermia; linear polyethylenimine; drug-delivery; xenograft model; DNA complexes; solid tumors; blood-flow; polyplexes; expression
ISSN (print) / ISBN
1043-0342
e-ISSN
1557-7422
Zeitschrift
Human Gene Therapy. Clinical Development
Quellenangaben
Band: 19,
Heft: 11,
Seiten: 1283-1292
Verlag
Mary Ann Liebert
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
CCG Tumor Therapy with Hyperthermia (IMI-KTH)