Non-covalent conjugates of single-walled carbon nanotubes and folic acid for interaction with cells over-expressing folate receptors

We here present a method to form a noncovalent conjugate of single-walled carbon nanotubes and folic acid aimed to interact with cells over-expressing folate receptors. The bonding was obtained without covalent chemical functionalization using a simple, rapid “one pot” synthesis method. The zeta potential for the single-walled carbon nanotube–folic acid solution was −32.4 mV at pH 7.0 and the result indicates that the folic acid coating inhibited aggregation of the carbon nanotubes. Properties of the single-walled carbon nanotube–folic acid conjugate were analyzed using ultraviolet-visible, fluorescence and Raman spectroscopies. While the folic acid fluorescence signature was significantly quenched by the presence of single-walled carbon nanotubes, the Raman spectra of the conjugate displayed a decreased distribution of sp3 sites. Both results were attributed to the noncovalent functionalization of the single-walled carbon nanotubes with folic acid. A more detailed investigation of the single-walled carbon nanotube–folic acid conjugates utilizing scanning electron microscopy, atomic force microscopy and energy-dispersive X-ray spectroscopy confirmed the presence of the well-defined folic acid coating on the individual single-walled carbon nanotubes. The single-walled carbon nanotube–folic acid conjugates were incubated with THP-1 cells and the internalization was evaluated by Giemsa staining with light microscopy, and cytotoxicity was evaluated using the MTT reduction assay. The cytotoxicity studies presented a low toxicity of the conjugates in the THP-1 cells. The low toxicity and the cellular uptake of single-walled carbon nanotube–folic acid by cancer cells suggest their potential use in carbon nanotube-based drug delivery systems and in the diagnosis of cancer or tropical diseases such as leishmaniasis.