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

Background: /Objectives: This paper reports the synthesis of TiO₂ nanoparticles, their functionalization with folic acid (FA), and loading with zinc phthalocyanine (ZnPc) to develop photosensitizers for photodynamic therapy applications against glioma cells. Methods: TiO₂, TiO₂-FA, and TiO₂-FA-ZnPc nanoparticles were obtained via the sol-gel process, involving hydrolysis and condensation of titanium (IV) isopropoxide. During these steps, FA and ZnPc were incorporated into the TiO₂ network in vitro. The resulting TiO₂-based materials were characterized using transmission and scanning electron microscopy, X-ray diffraction, Raman and UV-Vis spectroscopy, thermogravimetry, and nitrogen adsorption-desorption measurements. An in vitro study was also conducted using the 1,3-diphenylisobenzofuran (DPBF) probe to determine ROS generation by TiO₂. To achieve this, a 40-ppm solution was irradiated with UV light in the presence of each TiO₂ system. Biological assays involved evaluating the viability of LN18 and U251 (human glioblastoma) cells incubated with different TiO₂ systems, both with and without UV light irradiation. Results: Although TiO₂ retained its primary characteristics, such as a large surface area (around 600–700 m²/g), mesoporous structure (approximately 4–5 nm pore size), mixed anatase-amorphous morphology, and a bandgap of ~3.46 eV; each titania sample also displayed unique features. The UV-Vis spectrum of TiO₂-FA-ZnPc exhibited additional absorption bands in the visible range (600–700 nm). The characteristic DPBF absorption signal at 410 nm decreased gradually with irradiation time. Complete degradation of DPBF occurred in 10 minutes with TiO₂, 12 minutes with TiO₂-FA, and 14 minutes with TiO₂-FA-ZnPc. LN18 and U251 cells were not damaged by the presence of the materials alone at concentrations <100 μg/mL, in contrast to cells irradiated with UV light. Conclusions: Biocompatible materials with phototoxicity under UV light were successfully synthesized, making them promising candidates for application in photodynamic therapy.