PMID- 19866491 OWN - NLM STAT- MEDLINE DCOM- 20091110 LR - 20221021 IS - 1557-7422 (Electronic) IS - 1043-0342 (Linking) VI - 19 IP - 11 DP - 2008 Nov TI - Hyperthermia-induced targeting of thermosensitive gene carriers to tumors. PG - 1283-92 AB - 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. FAU - Schwerdt, Alenka AU - Schwerdt A AD - Pharmaceutical Biology-Biotechnology, Department of Pharmacy, Ludwig-Maximilians-Universitat, Munich, Germany. FAU - Zintchenko, Arkadi AU - Zintchenko A FAU - Concia, Massimo AU - Concia M FAU - Roesen, Nick AU - Roesen N FAU - Fisher, Kerry AU - Fisher K FAU - Lindner, Lars H AU - Lindner LH FAU - Issels, Rolf AU - Issels R FAU - Wagner, Ernst AU - Wagner E FAU - Ogris, Manfred AU - Ogris M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Hum Gene Ther JT - Human gene therapy JID - 9008950 RN - 0 (Polymers) RN - 0 (RNA, Messenger) RN - 9002-98-6 (Polyethyleneimine) RN - 9007-49-2 (DNA) RN - EC 1.13.12.- (Luciferases) SB - IM MH - Animals MH - DNA/*administration & dosage MH - *Gene Transfer Techniques MH - *Genetic Therapy MH - Genetic Vectors MH - Hindlimb/metabolism/pathology MH - *Hyperthermia, Induced MH - Immunoenzyme Techniques MH - Luciferases/metabolism MH - Male MH - Mice MH - Mice, Inbred A MH - Neuroblastoma/genetics/*therapy MH - Polyethyleneimine/chemistry MH - Polymers/*chemistry MH - RNA, Messenger/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Transfection MH - Transgenes/*physiology EDAT- 2009/10/30 06:00 MHDA- 2009/11/11 06:00 CRDT- 2009/10/30 06:00 PHST- 2009/10/30 06:00 [entrez] PHST- 2009/10/30 06:00 [pubmed] PHST- 2009/11/11 06:00 [medline] AID - 10.1089/hum.2008.064 [doi] PST - ppublish SO - Hum Gene Ther. 2008 Nov;19(11):1283-92. doi: 10.1089/hum.2008.064.