PMID- 20878655 OWN - NLM STAT- MEDLINE DCOM- 20110131 LR - 20101014 IS - 1613-6829 (Electronic) IS - 1613-6810 (Linking) VI - 6 IP - 20 DP - 2010 Oct 18 TI - Hybrid polymer-grafted multiwalled carbon nanotubes for in vitro gene delivery. PG - 2281-91 LID - 10.1002/smll.201000864 [doi] AB - Carbon nanotubes (CNTs) consist of carbon atoms arranged in sheets of graphene rolled up into cylindrical shapes. This class of nanomaterials has attracted attention because of their extraordinary properties, such as high electrical and thermal conductivity. In addition, development in CNT functionalization chemistry has led to an enhanced dispersibility in aqueous physiological media which indeed broadens the spectrum for their potential biological applications including gene delivery. The aim of this study is to determine the capability of different cationic polymer-grafted multiwalled carbon nanotubes (MWNTs) (polymer-g-MWNTs) to efficiently complex and transfer plasmid DNA (pCMV-betaGal) in vitro without promoting cytotoxicity. Carboxylated MWNT is chemically conjugated to the cationic polymers polyethylenimine (PEI), polyallylamine (PAA), or a mixture of the two polymers. In order to explore the potential of these polymer-g-MWNTs as gene delivery systems, we first study their capacity to complex plasmid DNA (pDNA) using agarose gel electrophoresis. Gel migration studies confirm pDNA binding to polymer-g-MWNT with different affinities, highest for PEI-g-MWNT and PEI/PAA-g-CNT constructs. beta-galactosidase expression is assessed in human lung epithelial (A549) cells, and the cytotoxicity is determined by modified LDH assay after 24 h incubation period. Additionally, PEI-g-MWNT and/or PEI/PAA-g-MWNT reveal an improvement in gene expression when compared to the naked pDNA or to the equivalent amounts of PEI polymer alone. Mechanistically, pDNA was delivered by the polymer-g-MWNT constructs via a different pathway compared to those used by polyplexes. In conclusion, polymer-g-MWNTs may be considered in the future as a versatile tool for efficient gene transfer in cancer cells in vitro, provided their toxicological profile is established. FAU - Nunes, Antonio AU - Nunes A AD - Nanomedicine Laboratory, Centre for Drug Delivery Research, The School of Pharmacy, University of London, UK. FAU - Amsharov, Nadja AU - Amsharov N FAU - Guo, Chang AU - Guo C FAU - Van den Bossche, Jeroen AU - Van den Bossche J FAU - Santhosh, Padmanabhan AU - Santhosh P FAU - Karachalios, Theodoros K AU - Karachalios TK FAU - Nitodas, Stephanos F AU - Nitodas SF FAU - Burghard, Marko AU - Burghard M FAU - Kostarelos, Kostas AU - Kostarelos K FAU - Al-Jamal, Khuloud T AU - Al-Jamal KT LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Small JT - Small (Weinheim an der Bergstrasse, Germany) JID - 101235338 RN - 0 (Nanotubes, Carbon) RN - 0 (Polyamines) RN - 0 (Polymers) RN - 30551-89-4 (polyallylamine) RN - 9002-98-6 (Polyethyleneimine) SB - IM MH - Cell Line, Tumor MH - Electrophoresis, Agar Gel MH - *Gene Transfer Techniques MH - Humans MH - Magnetic Resonance Spectroscopy MH - Microscopy, Electron, Scanning MH - Microscopy, Electron, Transmission MH - Nanomedicine/methods MH - Nanotubes, Carbon/*chemistry/ultrastructure MH - Plasmids/chemistry/genetics MH - Polyamines/chemistry MH - Polyethyleneimine/chemistry MH - Polymers/*chemistry MH - Spectrum Analysis, Raman EDAT- 2010/09/30 06:00 MHDA- 2011/02/01 06:00 CRDT- 2010/09/30 06:00 PHST- 2010/09/30 06:00 [entrez] PHST- 2010/09/30 06:00 [pubmed] PHST- 2011/02/01 06:00 [medline] AID - 10.1002/smll.201000864 [doi] PST - ppublish SO - Small. 2010 Oct 18;6(20):2281-91. doi: 10.1002/smll.201000864.