Rodríguez-Pérez Citlali Ekaterina, Rodríguez-García Sonia, Manríquez-Ramírez Ma Elena, Ortiz-Torres A Martin, Tzompantzi-Morales Francisco, Ortiz-Islas Emma
Laboratorio de Neurofarmacología Molecular y Nanotecnología, Instituto Nacional de Neurología y Neurocirugía, Insurgentes Sur 3877, La Fama, Tlalpan, Ciudad de México 14269, Mexico.
Facultad de Psicología, Universidad Nacional Autónoma de México-UNAM, Av. Universidad 3004, Copilco, Ciudad Universitaria, Ciudad de México 04510, Mexico.
Pharmaceutics. 2025 Aug 19;17(8):1071. doi: 10.3390/pharmaceutics17081071.
This study reports the synthesis of TiO 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. TiO, TiO-FA, and TiO-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 TiO 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 TiO-based materials, with and without UV exposure. Human fibroblast cells (BJ) were used to evaluate biocompatibility. All TiO-based materials retained key characteristics, including high surface area (~600-700 m/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 TiO-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 (TiO), 12 min (TiO-FA), and 14 min (TiO-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. The synthesized TiO-based systems demonstrate good biocompatibility and significant phototoxicity under UV irradiation, highlighting their strong potential for application in photodynamic therapy.
本研究报道了二氧化钛纳米颗粒的合成、其与叶酸(FA)的功能化以及随后负载锌酞菁(ZnPc)以开发用于靶向胶质瘤细胞的光动力疗法(PDT)的光敏剂。通过涉及异丙醇钛(IV)水解和缩合的溶胶 - 凝胶法合成了TiO、TiO - FA和TiO - FA - ZnPc纳米颗粒。在合成过程中于体外掺入FA和ZnPc。通过透射和扫描电子显微镜(TEM和SEM)、X射线衍射(XRD)、拉曼光谱和紫外 - 可见光谱、热重分析(TGA)以及氮吸附 - 脱附测量对所得材料进行表征。使用1,3 - 二苯基异苯并呋喃(DPBF)探针在体外评估活性氧(ROS)的产生。用紫外光照射每种TiO体系的40 ppm溶液,并监测DPBF的降解情况。进行生物学测定以评估与基于TiO的材料孵育且有或无紫外线照射的人胶质母细胞瘤细胞(LN18和U251)的活力。使用人成纤维细胞(BJ)评估生物相容性。所有基于TiO的材料都保留了关键特性,包括高比表面积(约600 - 700 m/g)、介孔结构(孔径约4 - 5 nm)、锐钛矿 - 非晶混合形态以及约3.46 eV的带隙。TiO - FA - ZnPc的紫外 -可见光谱在可见光区域(600 - 700 nm)显示出额外的吸收带,与ZnPc的掺入一致。在紫外照射下,DPBF在410 nm处的吸光度随时间降低,表明产生了ROS,并在10分钟(TiO)、12分钟(TiO - FA)和14分钟(TiO - FA - ZnPc)内完全降解。BJ细胞在所有浓度下均表现出良好的生物相容性。LN18和U251细胞在低于100μg/mL时无细胞毒性,除非暴露于紫外光下。合成的基于TiO的体系在紫外照射下表现出良好的生物相容性和显著的光毒性,突出了它们在光动力疗法中应用的强大潜力。