Single-Walled Carbon Nanotubes Targeted to the Tumor Vasculature for Breast Cancer Treatment

摘要

This project explores a novel treatment of breast cancer that uses single-walled carbon nanotubes (SWNTs) in photodynamic therapy, in which the SWNTs are targeted to the endothelial cells that line the tumor vasculature. The purpose of this project is to evaluate this treatment concept using human endothelial cells in vitro. Recombinant annexin V has been produced in good purity and high yield, and it has been shown to bind strongly to plastic- immobilized phosphatidylserine (PS), with a dissociation constant (Kd ) of 5.1 nM. A new method was developed for conjugating amino groups of annexin V to single-walled carbon nanotubes (SWNTs) that retains the strong absorbance of the SWNTs at 980 nm. This method uses the linker fluorenylmethoxycarbonyl (Fmoc)-amine-PEG-succinimidyl carboxy methyl ester. The loading of annexin V on the SWNTs was high (7.7 mg protein/mg SWNTs). Human endothelial cells grown in vitro could be killed almost completely when SWNT-Fmoc-PEG-annexin V was bound to the cells and with laser light at 980 nm and an energy density of 195 J/cm2. By contract, there was no harm to cells with SWNT-Fmoc-PEG-annexin V bound and no laser treatment, and there was no harm to cells with no SWNT-Fmoc-PEG- annexin V bound receiving laser treatment.