期刊
BIOCONJUGATE CHEMISTRY
卷 26, 期 7, 页码 1370-1379出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.5b00249
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- School of Pharmacy, University of London
- University of Trieste
- Italian Ministry of Education MIUR [cofin Prot. 20085M27SS, firb prot. RBAP11ETKA]
- Regione Friuli Venezia Giulia
- Centre National de la Recherche Scientifique (CNRS)
- European Union FP7 ANTICARB research programme [FP7-HEALTH-2007-2.4.1-7]
- ERC Advanced Grant Carbonano-bridge [ERC-2008-AdG-227135]
- Prostate Cancer UK [CDF12-002] Funding Source: researchfish
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 dancer therapy have been studied due to their ability to efficiently deliver siRNA intracellularly. In this study, we established the capacity of cationic MVVNT-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 siPLKEM4VNT-NH3+ complexes and their ability to significantly improve animal survival. Biological analysis of the siPLK1:MWNTNH3+ 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 MVVNT-NH3+, we established for the first tune 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.
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