Obtention and Characterization of TiO2-Folic Acid-ZnPc Semiconductor Nanoparticles for Photodynamic Therapy Against Glioma Cells

<b>Background/Objectives:</b> This study reports the synthesis of TiO₂ nanoparticles, their functionalization with folic acid (FA), and the subsequent loading with zinc phthalocyanine (ZnPc) to develop photosensitizers for photodynamic therapy (PDT) targeting glioma cells. <b>Methods:</b> TiO₂, TiO₂-FA, and TiO₂-FA-ZnPc nanoparticles were synthesized via a sol-gel process involving the hydrolysis and condensation of titanium (IV) isopropoxide. FA and ZnPc were incorporated in vitro during the synthesis. The resulting materials were characterized by transmission and scanning electron microscopy (TEM and SEM), X-ray diffraction (XRD), Raman and UV-Vis spectroscopy, thermogravimetric analysis (TGA), and nitrogen adsorption-desorption measurements. Reactive oxygen species (ROS) generation was evaluated in vitro using the 1,3-diphenylisobenzofuran (DPBF) probe. A 40 ppm solution of each TiO₂ system was irradiated with UV light, and the degradation of DPBF was monitored. Biological assays were conducted to assess the viability of human glioblastoma cells (LN18 and U251) incubated with the TiO₂-based materials, with and without UV exposure. Human fibroblast cells (BJ) were used to evaluate biocompatibility. <b>Results:</b> All TiO₂-based materials retained key characteristics, including high surface area (~600-700 m²/g), mesoporous structure (pore diameter ~4-5 nm), mixed anatase-amorphous morphology, and a bandgap of approximately 3.46 eV. The UV-Vis spectrum of TiO₂-FA-ZnPc displayed additional absorption bands in the visible region (600-700 nm), consistent with ZnPc incorporation. Upon UV irradiation, the DPBF absorbance at 410 nm decreased over time, indicating ROS generation and resulting in complete degradation within 10 min (TiO₂), 12 min (TiO₂-FA), and 14 min (TiO₂-FA-ZnPc). BJ cells exhibited good biocompatibility at all concentrations. LN18 and U251 cells showed no cytotoxicity below 100 μg/mL unless exposed to UV light. <b>Conclusions:</b> The synthesized TiO₂-based systems demonstrate good biocompatibility and significant phototoxicity under UV irradiation, highlighting their strong potential for application in photodynamic therapy.