Visible-light-responsive folate-conjugated titania and alumina nanotubes for photodynamic therapy applications

The use of nanomaterials in photodynamic therapy (PDT) has emerged as a promising alternative to enhance the efficacy and overcome the limitations of conventional photosensitizers. A major challenge in this regard is the development of novel cheap, synthetically convenient and biocompatible photoresponsive nanomaterials for visible-light-driven PDT applications. In this work, folate-conjugated titania and alumina nanotubes were successfully prepared and evaluated as novel photoactive nanomaterials with visible light responsiveness. Nanotubes were prepared by hydrothermal synthesis and surface-conjugated with folic acid using a silane coupling agent. Materials were characterized by ATR, TEM, XRD and TGA methods, and their photophysical properties were assessed from diffuse reflectance spectroscopy, production of reactive oxygen species (¹O₂ and HO^•) and confocal microscopy fluorescence emission experiments. Our results revealed that folate-conjugated titania and alumina nanotubes are photodynamically active upon irradiation with a blue-LED visible light source, whereas pristine nanotubes or free folic acid exhibits negligible photoresponse under the same experimental conditions. In vitro phototoxicity experiments on HeLa cancer cells confirmed the photodynamic efficacy of folate-conjugated materials as inhibitors of cell proliferation after 1 h of blue-LED light irradiation (450 nm, 100 W m⁻²) in 4 mg/mL solid suspensions. Folate-alumina nanotubes exhibited the highest activity within the nanomaterials under study, which—to the best of our knowledge—constitutes a major advance toward the use of alumina-based nanomaterials in visible-light-driven PDT applications.