Targeting and Photodynamic Killing of Cancer Cell by Nitrogen-Doped Titanium Dioxide Coupled with Folic Acid

Titanium dioxide (TiO₂) has attracted wide attention as a potential photosensitizer (PS) in photodynamic therapy (PDT). However, bare TiO₂ can only be excited by ultraviolet illumination, and it lacks specific targeting ligands, which largely impede its application. In our study, we produced nitrogen-doped TiO₂ and linked it with an effective cancer cell targeting agent, folic acid (FA), to obtain N-TiO₂-FA nanoconjugates. Characterization of N-TiO₂-FA included Zeta potential, absorption spectra and thermogravimetric analysis. The results showed that N-TiO₂-FA was successfully produced and it possessed better dispersibility in aqueous solution than unmodified TiO₂. The N-TiO₂-FA was incubated with human nasopharyngeal carcinoma (KB) and human pulmonary adenocarcinoma (A549) cells. The KB cells that overexpress folate receptors (FR) on cell membranes were used as FR-positive cancer cells, while A549 cells were used as FR-negative cells. Laser scanning confocal microscopy results showed that KB cells had a higher uptake efficiency of N-TiO₂-FA, which was about twice that of A549 cells. Finally, N-TiO₂-FA is of no cytotoxicity, and has a better photokilling effect on KB cells under visible light irradiation. In conclusion, N-TiO₂-FA can be as high-value as a PS in cancer targeting PDT.