Small, 2009, 5 (10):1176 - 1185
Antitumor activity and prolonged survival by carbon nanotube-mediated therapeutic siRNA silencing in a human lung xenograft model
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-NHþ3). 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-NHþ3 in vitro. A comparative study using both types of vector indicates that only MWNT-NHþ3 :siRNA complexes administered intratumorally can elicit delayed tumor growth and increased survival of xenograft-bearing animals. siTOX delivery via the cationic MWNT-NHþ3 is biologically active in vivo by triggering an apoptotic cascade, leading to extensive necrosis of the human tumor mass.