期刊
NATURE NANOTECHNOLOGY
卷 8, 期 10, 页码 763-771出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nnano.2013.190
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资金
- National Institutes of Health [NIH P01 CA33049, NIH R01 CA55349, R21 CA128406]
- Office of Science (BER), the US Department of Energy [DE-SC0002456]
- NIH Medical Scientist Training Program (MSTP) [GM07739]
- MSKCC Molecular Cytology Core Facility
- MSKCC Experimental Therapeutics Center
- MSKCC Brain Tumour Center
- Tudor Fund
- Glades Fund
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 antibodynanotube 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 Ac-225 were found to clear rapidly, thus mitigating radioisotope toxicity, and were shown to be therapeutically effective in vivo
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