Double Impact of Modified Single-Walled Carbon Nanotubes in Nanomedicine: Vehicles for Gene Therapy and Theranostic Agents

Monday, May 12, 2014: 10:20
Bonnet Creek Ballroom X, Lobby Level (Hilton Orlando Bonnet Creek)
S. Alidori, J. J. Mulvey, M. R. McDevitt, and D. A. Scheinberg (Departments of Medicine, Radiology, and the Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065.)
In this work we demonstrated that single-walled carbon nanotubes (SWNTs) can be successfully exploited as tools to effectively deliver imaging agents, drugs or genetic material to tumors or selected tissues and offer significant advantages over antibody-based approaches or if compared to other nano-materials. In particular, the nanotubes can carry a substantial amount of cargo as compared to a monoclonal antibody, but can still be rapidly eliminated from the circulation by renal filtration, like a small molecule, due to their high aspect ratio, a property distinct from other nanoparticles. We describe how chemically modified SWCNTs can be used to stabilize, transport and deliver siRNA inside cells in vitro and in vivo in mice, allowing for the knockdown of specific genes. The optimization of SWCNTs and RNA constructs is essential for specific and efficient systemic delivery of gene-vectors to cellular targets. Our results have been applied to constructs that were able to silence the expression of protein more effectively and with lower cytotoxicity than a conventional transfecting agent, in vitro and in vivo.  A second strategy involves the use of SWCNTs as multimodal platforms to target tumors in a two-step approach in which nanotubes modified with morpholino oligonucleotide sequences bind to cancer cells after pre-targeting with antibodies modified with complementary morpholino sequences. The nanotubes can carry fluorophores or radioisotopes, and are shown to selectively bind to and kill cancer cells in vitro and in tumour-bearing xenografted mice. Furthermore, the in vivo assembled constructs were demonstrated to internalize inside the targeted cancer cells. Conjugates labeled with alpha-particle-generating 225Ac were found to clear rapidly, thus mitigating radioisotope toxicity, and were shown to be therapeutically effective in vivo. Finally, the nanotube conjugates were labeled with both alpha-particle and gamma-ray emitting isotopes, at high specific activities, showing their potential use as powerful theranostic agents.