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Open Access Green as soon as Postprint is submitted to ZB.
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
in-vivo; local hyperthermia; linear polyethylenimine; drug-delivery; xenograft model; DNA complexes; solid tumors; blood-flow; polyplexes; expression
Language
english
Publication Year
2008
HGF-reported in Year
2008
ISSN (print) / ISBN
1043-0342
e-ISSN
1557-7422
Quellenangaben
Volume: 19,
Issue: 11,
Pages: 1283-1292
Publisher
Mary Ann Liebert
Reviewing status
Peer reviewed
Institute(s)
CCG Tumor Therapy with Hyperthermia (IMI-KTH)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Immune Response and Infection
PSP Element(s)
G-521100-001
Scopus ID
57049108286
Erfassungsdatum
2008-12-31