Enhanced cellular internalization and gene silencing with a series of cationic dendron-multiwalled carbon nanotube:siRNA complexes

Al-Jamal K. T., Toma F. M., Yilmazer A., Ali-Boucetta H., Nunes A., Herrero M., ...More

FASEB JOURNAL, vol.24, no.11, pp.4354-4365, 2010 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 24 Issue: 11
  • Publication Date: 2010
  • Doi Number: 10.1096/fj.09-141036
  • Journal Name: FASEB JOURNAL
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.4354-4365
  • Keywords: RNA interference, gene transfer, knockdown, nanotechnology, nonviral, SMALL INTERFERING RNA, INTRACELLULAR DELIVERY, PLASMID DNA, SIRNA, TRANSPORTERS, APOPTOSIS, FUNCTIONALIZATION, NANOMATERIALS, CYTOTOXICITY, BINDING
  • Ankara University Affiliated: No

Abstract

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.-Al-Jamal, K. T., Toma, F. M., Yilmazer, A., Ali-Boucetta, H., Nunes, A., Herrero, M.-A., Tian, B., Eddaoui, A., Al-Jamal, W. T., Bianco, A., Prato, M., Kostarelos, K. Enhanced cellular internalization and gene silencing with a series of cationic dendron-multiwalled carbon nanotube:siRNA complexes. FASEB J. 24, 4354-4365 (2010). www.fasebj.org