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Schwerdt, A.* ; Zintchenko, A.* ; Concia, M.* ; Roesen, N.* ; Fisher, K.* ; Lindner, L.H. ; Issels, R.D. ; Wagner, E.* ; Ogris, M.*

Hyperthermia-induced targeting of thermosensitive gene carriers to tumors.

Hum. Gene Ther. 19, 1283-1292 (2008)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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
Sprache englisch
Veröffentlichungsjahr 2008
HGF-Berichtsjahr 2008
ISSN (print) / ISBN 1043-0342
e-ISSN 1557-7422
Quellenangaben Band: 19, Heft: 11, Seiten: 1283-1292 Artikelnummer: , Supplement: ,
Verlag Mary Ann Liebert
Begutachtungsstatus Peer reviewed
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-521100-001
Scopus ID 57049108286
Erfassungsdatum 2008-12-31