Self-assembly of carbon nanotubes and antibodies on tumours for targeted amplified delivery.
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.
1] Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA [2] Weill-Cornell Medical College, 468 East 68th Street, New York, New York 10065, USA [3].
J Justin
JJ
Mulvey
Carlos H
CH
Villa
Michael R
MR
McDevitt
Freddy E
FE
Escorcia
Emily
E
Casey
David A
DA
Scheinberg
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D051379:Mice; D060172:Morpholinos / Q000737:chemistry; D037742:Nanotubes, Carbon / Q000737:chemistry*; D009369:Neoplasms / Q000628:therapy; D011868:Radioisotopes / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D060172:Morpholinos; D037742:Nanotubes, Carbon; D011868:Radioisotopes