1. Enhanced cellular internalization and gene silencing with a series of cationic dendron-multiwalled carbon nanotube:siRNA complexes
- Author
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Francesca M. Toma, Khuloud T. Al-Jamal, Wafa' T Al-Jamal, Ayad Eddaoudi, Kostas Kostarelos, Alberto Bianco, Maria-Antonia Herrero, Antonio Nunes, Maurizio Prato, Açelya Yilmazer, Bowen Tian, Hanene Ali-Boucetta, Nanomedicine Laboratory, Queen Mary University of London (QMUL), Center of Excellence for Nanostructured Materials, University of Trieste, Departamento de Quimica Organica, Universidad de Castilla-La Mancha (UCLM), Flow Cytometry Core Facility, University College of London [London] (UCL), Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), ANR-05-JCJC-0031-01,ANR-05-JCJC-0031-01, K. T., Al Jamal, F. M., Toma, A., Yilmazer, H., Ali Boucetta, A., Nune, M. A., Herrero, B., Tian, A., Eddaoui, A. J. W., T., A., Bianco, Prato, Maurizio, and K., Kostarelos
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Models, Molecular ,Small interfering RNA ,MESH: Cell Line, Tumor ,Cell Survival ,MESH: Biological Transport ,02 engineering and technology ,Biology ,Transfection ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Cell Line ,[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication ,RNA interference ,Cations ,Cell Line, Tumor ,MESH: RNA, Small Interfering ,Genetics ,Humans ,Gene silencing ,MESH: Gene Silencing ,Gene Silencing ,RNA, Small Interfering ,MESH: Cations ,Cytotoxicity ,Molecular Biology ,Gene knockdown ,MESH: Humans ,carbon nanotubes ,Nanotubes, Carbon ,MESH: Transfection ,RNA ,Biological Transport ,021001 nanoscience & nanotechnology ,MESH: Cell Line ,0104 chemical sciences ,Cell biology ,MESH: Hela Cells ,MESH: Cell Survival ,MESH: Nanotubes, Carbon ,Drug delivery ,0210 nano-technology ,MESH: Models, Molecular ,HeLa Cells ,Biotechnology - Abstract
International audience; One of the major obstacles to the clinical development of gene silencing by small interfering RNA (siRNA) is its effective cytoplasmic delivery. Carbon nanotubes have been proposed as novel nanomaterials that can offer significant advantages for the intracellular delivery of nucleic acids, such as siRNA. We recently demonstrated in a proof-of-principle study that amino-functionalized multiwalled carbon nanotubes (f-MWNT) can effectively deliver in vivo an siRNA sequence, triggering cell apoptosis that results in human lung xenograft eradication and prolonged survival. In the present study, we demonstrate how a newly synthesized series of polycationic dendron-MWNT constructs with a precisely tailored number of amino functions (dendron generations) can complex and effectively deliver double-stranded siRNA to achieve gene silencing in vitro. A systematic comparison between the f-MWNT series in terms of cellular uptake, cytotoxicity, and siRNA complexation is offered. Significant improvement in siRNA delivery with the dendron-MWNT conjugates is shown, and gene silencing was obtained in 2 human cell lines using 2 different siRNA sequences. The study reveals that through f-MWNT structure-biological function analysis novel nanotube-based siRNA transfer vectors can be designed with minimal cytotoxicity and effective delivery and gene-silencing capabilities.
- Published
- 2010
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