Applications of carbon nanotubes in cancer immunotherapy

Most systemic anti-cancer therapies lack specificity and have considerable toxicities. There is great interest in improving specificity through better delivery of cytotoxic agents or through more specific immunologic interventions. The field of nanomedicine aims to exploit the unique sizes and shapes of synthetic nanoscale particles to address this challenge. Because the physical scale of nanomaterials is of the same order of proteins and viruses, it is believed nanoparticles offer the potential to better control biologic interactions at this scale, and ultimately to tune properties such as pharmacokinetics, pharmacodynamics, immunogenicity, and cellular trafficking. Hence, carbon nanotubes have drawn considerable attention in biomedical applications. Carbon nanotubes are graphene cylinders composed entirely of carbon atoms. Here, we explore single-walled carbon nanotubes (SWNT) that are only 1--2 nm in diameter, while having lengths of several hundred nanometers. It is believed that the unique physical characteristics of carbon nanotubes (high aspect ratio, all carbon backbone, and robust chemical stability) result in unique biologic properties.;In order to apply carbon nanotubes in biologic systems we covalently functionalized SWNT to render them water dispersible and to mitigate toxicity associated with insoluble, microscale aggregates. After chemical functionalization, several different biomolecules were appended to the nanotube surface to confer biologic activity. In the current studies, we aimed to append short oligonucleotides to the nanotubes to give them the ability to recognize complementary sequences. We show that oligonucleotide functionalized carbon nanotubes maintain their pharmacokinetic properties, can hybridize complementary oligonucleotide sequences, and can be appended with radioisotopes and targeting peptides. We also demonstrate that oligonucleotide functionalized SWNT can be effective carriers in a pretargeted approach to radioimmunotherapies, and that SWNT can self-assemble onto a range of tumor types in the presence of human serum and in animal models. This approach aims to take advantage of the rapid renal clearance of SWNT. Finally, we performed immunologic studies to explore the potential of SWNT as antigen carriers for cancer vaccination strategies. We characterized the interaction with antigen presenting cells, and demonstrated that SWNT can improve antibody responses to appended weakly immunogenic peptides. These studies serve as a foundation for future development of carbon nanotubes in the field of radioimmunotherapy and cancer vaccines.