TY - JOUR
T1 - Self-assembly of carbon nanotubes and antibodies on tumours for targeted amplified delivery
AU - Mulvey, J. Justin
AU - Villa, Carlos H.
AU - McDevitt, Michael R.
AU - Escorcia, Freddy E.
AU - Casey, Emily
AU - Scheinberg, David A.
N1 - Funding Information:
The authors acknowledge support from the National Institutes of Health (NIH P01 CA33049 to D.A.S.; NIH R01 CA55349 to D.A.S.; R21 CA128406 to M.R.M.), the Office of Science (BER), the US Department of Energy (award no. DE-SC0002456 to M.R.M.), the NIH Medical Scientist Training Program (MSTP; grant GM07739 to J.J.M., C.H.V. and F.E.E.), the MSKCC Molecular Cytology Core Facility, the MSKCC Experimental Therapeutics Center, the MSKCC Brain Tumour Center and The Tudor and Glades Funds. The authors thank D. Hnatowich for helpful discussions. The authors also thank W. Maguire, S. Alidori and E. Feinberg for assistance, Actinium Pharmaceuticals for 225Ac acquisition, and M. Bergkvist for TEM and Raman spectroscopy.
PY - 2013/10
Y1 - 2013/10
N2 - Single-walled carbon nanotubes (SWNTs) can deliver imaging agents or drugs to tumours and offer significant advantages over approaches based on antibodies or other nanomaterials. In particular, the nanotubes can carry a substantial amount of cargo (100 times more than 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. Here we show that SWNTs can target tumours in a two-step approach in which nanotubes modified with morpholino oligonucleotide sequences bind to cancer cells that have been pretargeted with antibodies modified with oligonucleotide strands complementary to those on the nanotubes. The nanotubes can carry fluorophores or radioisotopes, and are shown to selectively bind to cancer cells in vitro and in tumour-bearing xenografted mice. The binding process is also found to lead to antigen capping and internalization of the antibody-nanotube complexes. The nanotube conjugates were labelled with both alpha-particle and gamma-ray emitting isotopes, at high specific activities. Conjugates labelled with alpha-particle-generating 225 Ac were found to clear rapidly, thus mitigating radioisotope toxicity, and were shown to be therapeutically effective in vivo.
AB - Single-walled carbon nanotubes (SWNTs) can deliver imaging agents or drugs to tumours and offer significant advantages over approaches based on antibodies or other nanomaterials. In particular, the nanotubes can carry a substantial amount of cargo (100 times more than 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. Here we show that SWNTs can target tumours in a two-step approach in which nanotubes modified with morpholino oligonucleotide sequences bind to cancer cells that have been pretargeted with antibodies modified with oligonucleotide strands complementary to those on the nanotubes. The nanotubes can carry fluorophores or radioisotopes, and are shown to selectively bind to cancer cells in vitro and in tumour-bearing xenografted mice. The binding process is also found to lead to antigen capping and internalization of the antibody-nanotube complexes. The nanotube conjugates were labelled with both alpha-particle and gamma-ray emitting isotopes, at high specific activities. Conjugates labelled with alpha-particle-generating 225 Ac were found to clear rapidly, thus mitigating radioisotope toxicity, and were shown to be therapeutically effective in vivo.
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U2 - 10.1038/nnano.2013.190
DO - 10.1038/nnano.2013.190
M3 - Article
C2 - 24077028
AN - SCOPUS:84885481781
SN - 1748-3387
VL - 8
SP - 763
EP - 771
JO - Nature Nanotechnology
JF - Nature Nanotechnology
IS - 10
ER -