This article describes the preparation of a graphene electrode modified with a new conjugate of peptide nanotubes and folic acid for the selective detection of human cervical cancer cells over-expressing folate receptors. The functionalization of peptide nanotubes with folic acid was confirmed by fluorescence microscopy and atomic force microscopy. The peptide nanotube–folic acid modified graphene electrode was characterized by scanning electron microscopy and cyclic voltammetry. The modification of the graphene electrode with peptide nanotube–folic acid led to an increase in the current signal. The human cervical cancer cells were bound to the modified electrode through the folic acid–folate receptor interaction. Cyclic voltammograms in the presence of [Fe(CN)₆]^3−/4− as a redox species demonstrated that the binding of the folate receptor from human cervical cancer cells to the peptide nanotube–folic acid modified electrode lowered the electron transfer resulting in a decrease in the measured current. A detection limit of 250 human cervical cancer cells per mL was obtained. Control experiments confirmed that the peptide nanotube–folic acid electrode specifically recognized folate receptors. The modified electrode described here opens up new possibilities for future applications in early stage diagnoses of diseases where cells over-express folate receptors, such as in cancer or leishmaniasis disease.

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.