Design of Cationic Multi-Walled Carbon Nanotubes as Efficient siRNA Vectors for Lung Cancer Xenograft Eradication

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

Research output: Contribution to journalArticlepeer-review

62 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 intratumoural 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 RT-PCR and Western blot, in addition to TUNEL staining confirmed the biological functionality of the siRNA intratumourally, suggesting that tumor eradication was due to PLK1 knockdown. Furthermore, by using a fluorescently labelled, non-coding 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
JournalBioconjugate Chemistry
DOIs
Publication statusPublished - 3 Jun 2015

Fingerprint

Dive into the research topics of 'Design of Cationic Multi-Walled Carbon Nanotubes as Efficient siRNA Vectors for Lung Cancer Xenograft Eradication'. Together they form a unique fingerprint.

Cite this