Tumor Targeting with Antibody-Functionalized, Radiolabeled Carbon Nanotubes

Abstract

Single-walled carbon nanotubes (CNT) are mechanically robust graphene cylinders with a high aspect ratio that are comprised of sp 2 -bonded carbon atoms and possessing highly regular structures with defined periodicity. CNT exhibit unique mechanochemical properties that can be exploited for the development of novel drug delivery platforms. We hypothesized that novel prototype nanostructures consisting of biologics, radionuclides, fluorochromes, and CNT could be synthesized and designed to target tumor cells. Methods: Tumor-targeting CNT constructs were synthesized from sidewall-functionalized, water-soluble CNT platforms by covalently attaching multiple copies of tumorspecific monoclonal antibodies, radiometal-ion chelates, and fluorescent probes. The constructs were characterized spectroscopically, chromatographically, and electrophoretically. The specific reactivity of these constructs was evaluated in vitro by flow cytometry and cell-based immunoreactivity assays and in vivo using biodistribution in a murine xenograft model of lymphoma. Results: A soluble, reactive CNT platform was used as the starting point to build multifunctional constructs with appended antibody, metal-ion chelate, and fluorescent chromophore moieties to effect specific targeting, to carry and deliver a radiometal-ion, and to report location, respectively. These nanoconstructs were found to be specifically reactive with the human cancer cells they were designed to target in vivo in a model of disseminated human lymphoma and in vitro by flow cytometry and cell-based immunoreactivity assays versus appropriate controls. Conclusion: The key achievement in these studies was the selective targeting of tumor in vitro and in vivo by the use of specific antibodies appended to a soluble, nanoscale CNT construct. The ability to specifically target tumor with prototype-radiolabeled or fluorescent-labeled, antibody-appended CNT constructs was encouraging and suggested further investigation of CNT as a novel delivery platform.

Noninvasive molecular imaging of small living subjects using Raman spectroscopy

“…Unlike the SERS nanoparticles, these SWNTs are inherently Raman active and do not use a metal surface enhancer to increase Raman detection. The high aspect ratio of the carbon structure of SWNTs is ideal for bioconjugation, and recent reports have successfully shown specific tumor targeting in vivo within various tumor models, using various functionalized SWNTs (10,13,14). SWNTs have a very small diameter of Ϸ3 nm and a length of 200 nm, as schematically shown in Fig.…”

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

“…These novel carriers have the ability of cross the plasma membrane and enter into the cancerous cells (by endocytosis or penetration like a needle), having no influence the type of functionalization of the nanotubes or the type of cancer cells [298,299]. In addition, the functionalized surface of the nanotubes can be bound to different targeting moieties, leading to an enhanced tumor cell specificity of the cytotoxic agents, compared with the non-targeted carbon nanocarriers, and overcoming the multidrug resistance [300][301][302][303][304][305][306].…”

Novel role of nanotechnology in medicine

“…Cell specificity can be achieved by conjugating antibodies to carbon nanotubes with fluorescent or radiolabelling. 17 Entry of nanotubes into the cells may be mediated by endocytosis or by insertion through the cell membrane.…”