Design of Cationic Multiwalled Carbon Nanotubes as Efficient siRNA Vectors for Lung Cancer Xenograft Eradication

Yong Chang Guo, Wafa T Al-Jamal, Francesca M Toma, Alberto Bianco, Maurizio Prato, Khuloud T Al-Jamal, Kostas Kostarelos

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Polo-Like Kinase (PLK1) has been identified as a potential target in cancer gene therapy via chemical or genetic inhibitory approaches. The biomedical applications of chemically functionalized carbon nanotubes (f-CNTs) in cancer therapy have been studied due to their ability to efficiently deliver siRNA intracellularly. In this study, we established the capacity of cationic MWNT-NH3(+) to deliver the apoptotic siRNA against PLK1 (siPLK1) in Calu6 tumor xenografts by direct intratumoral injections. A direct comparison with cationic liposomes was made. This study validates the PLK1 gene as a potential target in cancer gene therapy including lung cancer, as demonstrated by the therapeutic efficacy of siPLK1:MWNT-NH3(+) complexes and their ability to significantly improve animal survival. Biological analysis of the siPLK1:MWNT-NH3(+) treated tumors by qRT-PCR and Western blot, in addition to TUNEL staining confirmed the biological functionality of the siRNA intratumorally, suggesting that tumor eradication was due to PLK1 knockdown. Furthermore, by using a fluorescently labeled, noncoding siRNA sequence complexed with MWNT-NH3(+), we established for the first time that the improved therapeutic efficacy observed in f-CNT-based siRNA delivery is directly proportional to the enhanced siRNA retention in the solid tumor and subsequent uptake by tumor cells after local administration in vivo.

Original languageEnglish
Pages (from-to)1370-1379
JournalBioconjugate Chemistry
Volume26
Issue number7
DOIs
Publication statusPublished - 15 Jul 2015
Externally publishedYes

Keywords

  • Animals
  • Apoptosis
  • Cations
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Female
  • Genetic Vectors
  • Humans
  • Lung
  • Lung Neoplasms
  • Mice, Nude
  • Nanotubes, Carbon
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • RNA Interference
  • RNA, Small Interfering
  • RNAi Therapeutics
  • Journal Article
  • Research Support, Non-U.S. Gov't

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