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

Khuloud T Al-Jamal, Francesca M Toma, Açelya Yilmazer, Hanene Ali-Boucetta, Antonio Nunes, Maria-Antonia Herrero, Bowen Tian, Ayad Eddaoudi, Ayad Eddaoui, Wafa' T Al-Jamal, Alberto Bianco, Maurizio Prato, Kostas Kostarelo

Research output: Contribution to journalArticle

65 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4354-65
Number of pages12
JournalThe FASEB Journal
Volume24
Issue number11
DOIs
Publication statusPublished - Nov 2010

Keywords

  • Biological Transport
  • Cations
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival
  • Gene Silencing
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Nanotubes, Carbon
  • RNA, Small Interfering
  • Transfection
  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint Dive into the research topics of 'Enhanced cellular internalization and gene silencing with a series of cationic dendron-multiwalled carbon nanotube:siRNA complexes'. Together they form a unique fingerprint.

  • Cite this

    Al-Jamal, K. T., Toma, F. M., Yilmazer, A., Ali-Boucetta, H., Nunes, A., Herrero, M-A., Tian, B., Eddaoudi, A., Eddaoui, A., Al-Jamal, W. T., Bianco, A., Prato, M., & Kostarelo, K. (2010). Enhanced cellular internalization and gene silencing with a series of cationic dendron-multiwalled carbon nanotube:siRNA complexes. The FASEB Journal, 24(11), 4354-65. https://doi.org/10.1096/fj.09-141036