Ultra-short carbon nanotubes as nanocapsules for medical imaging and therapy
Hartman, Keith Bennett
Wilson, Lon J.
Doctor of Philosophy
This thesis details the development of ultra-short, single-walled carbon nanotubes (US-tubes) for use as nanocapsules to contain and deliver medical agents for both imaging (Gd3+ ) and therapeutic (211 At) purposes. In particular, Gd3+ -loaded US-tubes, known as gadonanotubes, operate as high-performance MRI contrast agents with relaxivities (image enhancement efficacy) a factor of 40-100 greater than current clinical contrast agents. Furthermore, gadonanotube relaxivities are highly pH-dependent, with image intensity nearly tripling from pH 7.5 to 6.8. Coupled with their high efficacies and targeting potential, these agents are promising candidates for next-generation targeted imaging probes for the early detection of cancer. Single gadonanotubes have also been encapsulated in a polymer shell for use as an intravenous MRI contrast agent. In addition, a new functionalization scheme has been developed to covalently attach a variety of amino acids in high quantity to the outer surface of the gadonanotubes and to attach a small peptide sequence for targeting breast cancer cells. The gadonanotubes have also been used as magnetic cell labeling agents, while also demonstrating efficacy in vivo as contrast agents. In addition to functioning as an imaging agent platform, the US-tubes have demonstrated efficacy as nanocapsules for radiotherapeutic agents. Astatine-211 (At-211), an α-emitting radionuclide, can be loaded inside the US-tube with excellent containment stability for the targeted delivery of an α-radiotherapeutic agent to micrometastatic and single-cell cancers. The loading levels for At-211 are comparable to, or better than, other known compounds. At-211, existing as the mixed-halogen compound 211 AtCl, is retained in the US-tube nanocapsules due to van der Waals forces between the 211AtCl and the interior sidewalls of the nanotube. Finally, the US-tubes have been shown to induce few health risks in mammalian experiments. Acute toxicity tests were conducted on mice with both raw and purified full-length carbon nanotubes (SWNTs), as well as US-tubes, using large doses (up to 1 g/kg of bodyweight). Even at these large doses, no animal death was recorded, although in a few cases behavioral changes were observed. Nanotubes were observed to be eliminated from the liver and kidneys through the urine and feces. It is believed that any toxicity at high doses can be attenuated (and prevented) by properly formulating the administered dose.