Targeted nanomaterials for radiotherapy.
Academic Article
Overview
abstract
The single-walled carbon nanotube-111In-labeled1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid -rituximab (CNT-([111In]DOTA)(rituximab) is a nanoconstruct with multiple copies of the 111In-labeled DOTA chelate and anti-CD20 monoclonal antibody (MAb) independently attached covalently to the CNT-sidewall and can be used for imaging lymphoid malignancies (1). The CD20 antigen is a 35-kDa, nonglycosylated, cell-surface hydrophobic phosphoprotein expressed on normal and malignant B cells (2-4). It is a transmembrane protein that acts as a calcium channel and plays an important role in cell cycle progression and differentiation of B cells. CD20 is present on >90% of B cells from blood and lymphoid organs. Lymphoma cells from >90% of patients with B-cell non-Hodgkin lymphoma (NHL) expressed this antigen. When antibodies bind to this antigen, they may induce apoptosis, antibody-dependent cellular cytotoxicity, and complement-dependent cytotoxicity of lymphoma cells. Despite the presence of CD20 on normal B cells, it was proven to be an excellent tumor target for molecular targeting with antibodies for the management of NHL. Radiolabeled MAbs have been developed for both diagnosis and therapy of tumors (2, 5, 6). Rituximab (unlabeled chimeric 2B8 MAb) was constructed and approved by the United States Food and Drug Administration for use in NHL therapy (7, 8). Later, ibritumomab (intact murine anti-CD20 MAb), was labeled with 111In or 90Y for NHL imaging and therapy (9, 10). One limitation of radiolabeled MAbs is that only a small number of chelating moieties can be attached to each MAb molecule before the targeting capability is compromised and further, only a fraction of these chelates actually contain radionuclide (11, 12). As part of the development of nanotechnology, carbon nanotubes (CNTs) (13-16) are essentially hexagonal networks of carbon atoms arranged like a layer of graphite rolled into a cylinder. There are single-walled CNTs (SWNT) with only a single layer and multi-walled CNTs (MWNT) with many layers. Both SWNT and MWNT may possess lengths up to tens of micrometers and diameters between a few nanometers and hundreds of nanometers. There are numerous potential applications of CNTs in medicine. For example, the integration of CNTs and biomolecules provides a novel platform to deliver a therapeutic or diagnostic “payload” to a molecular target (1, 17-19). A major advantage of SWNTs is that all carbon atoms are surface atoms that provide many potential attachment sites for appending various ligands and an enormous aspect ratio permitting the attachment of multiple copies of different moieties (1). Although there are some concerns about the toxic potential of CNTs (20), soluble, nonaggregated, functionalized CNTs appear to be nontoxic to the biological system (21, 22). McDevitt et al. (1) first reported the synthesis of a single-walled CNT-([111In]DOTA)(rituximab) construct appended with multiple copies of DOTA chelate and antibodies to specifically target the CD20 epitope on human Burkitt lymphoma cells.
