Antitumor activity and prolonged survival by carbon-nanotube-mediated therapeutic sirna silencing in a human lung xenograft model

Jennifer E. Podesta, Khuloud T. Al-Jamal, Maria A. Herrero, Bowen Tian, Hanene Ali-Boucetta, Vikas Hegde, Alberto Bianco, Maurizio Prato, Kostas Kostarelos

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Carbon nanotubes are novel nanomaterials that are thought to offer potential benefits to a variety of biomedical and clinical applications. In this study, the treatment of a human lung carcinoma model in vivo using siRNA sequences leading to cytotoxicity and cell death is carried out using either cationic liposomes (DOTAP:cholesterol) or amino-functionalized multiwalled carbon nanotubes (MWNT-NH3+). Validation for the most cytotoxic siRNA sequence using a panel of human carcinoma and murine cells reveals that the proprietary siTOX sequence is human specific and can lead to significant cytotoxic activities delivered both by liposome or MWNT-NH 3+ in vitro. A comparative study using both types of vector indicates that only MWNT-NH3+:siRNA complexes administered intratumorally can elicit delayed tumor growth and increased survival of xenograft-bearing animals. siTOX delivery via the cationic MWNT-NH3+ is biologically active in vivo by triggering an apoptotic cascade, leading to extensive necrosis of the human tumor mass. This suggests that carbon-nanotube-mediated delivery of siRNA by intratumoral administration leads to successful and statistically significant suppression of tumor volume, followed by a concomitant prolongation of survival of human lung tumor-bearing animals. The direct comparison between carbon nanotubes and liposomes demonstrates the potential advantages offered by carbon nanotubes for the intracellular delivery of therapeutic agents in vivo. The present work may act as the impetus for further studies to explore the therapeutic capacity of chemically functionalized carbon nanotubes to deliver siRNA directly into the cytoplasm of target cells and achieve effective therapeutic silencing in various disease indications where local delivery is feasible or desirable. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.
    Original languageEnglish
    Pages (from-to)1176-1185
    Number of pages9
    JournalSmall
    Volume5
    Issue number10
    DOIs
    Publication statusPublished - 18 May 2009

    Keywords

    • Cancer therapy
    • Carbon nanotubes
    • Gene therapy
    • Liposomes
    • RNA interference

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