Diz Fernando Mendonça, Monteiro Wesley F, Silveira Iury Santos, Ruano Daniel, Zotti Eduardo Rosa, Weimer Rafael Diogo, Melo Micael Nunes, Schossler Lopes João Gabriel, Scheffel Thamiris Becker, Caldas Linda V E, da Costa Jaderson Costa, Morrone Fernanda Bueno, Ligabue Rosane Angélica
Preclinical Research Center, Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul-PUCRS, Porto Alegre, Rio Grande do Sul 90619-900, Brazil.
Graduate Program in Materials Engineering and Technology, Pontifical Catholic University of Rio Grande do Sul-PUCRS, Porto Alegre, Rio Grande do Sul 90619-900, Brazil.
ACS Omega. 2024 Jun 28;9(27):29499-29515. doi: 10.1021/acsomega.4c02125. eCollection 2024 Jul 9.
Radiotherapy (RT) is the established noninvasive treatment for glioblastoma (GBM), a highly aggressive malignancy. However, its effectiveness in improving patient survival remains limited due to the radioresistant nature of GBM. Metal-based nanostructures have emerged as promising strategies to enhance RT efficacy. Among them, titanate nanotubes (TNTs) have gained significant attention due to their biocompatibility and cost-effectiveness. This study aimed to synthesize zinc-modified TNTs (ZnTNT) from sodium TNTs (NaTNT), in addition to characterizing the formed nanostructures and evaluating their radiosensitization effects in GBM cells (U87 and U251). Hydrothermal synthesis was employed to fabricate the TNTs, which were characterized using various techniques, including transmission electron microscopy (TEM), energy-dispersive spectroscopy, scanning-transmission mode, Fourier-transform infrared spectroscopy, ICP-MS (inductively coupled plasma mass spectrometry), X-ray photoelectron spectroscopy, and zeta potential analysis. Cytotoxicity was evaluated in healthy (Vero) and GBM (U87 and U251) cells by the MTT assay, while the internalization of TNTs was observed through TEM imaging and ICP-MS. The radiosensitivity of ZnTNT and NaTNT combined with 5 Gy was evaluated using clonogenic assays. Monte Carlo simulations using the MCNP6.2 code were performed to determine the deposited dose in the culture medium for RT scenarios involving TNT clusters and cells. The results demonstrated differences in the dose deposition values between the scenarios with and without TNTs. The study revealed that ZnTNT interfered with clonogenic integrity, suggesting its potential as a powerful tool for GBM treatment.
放射疗法(RT)是胶质母细胞瘤(GBM)既定的非侵入性治疗方法,GBM是一种高度侵袭性的恶性肿瘤。然而,由于GBM的放射抗性,其在提高患者生存率方面的有效性仍然有限。金属基纳米结构已成为增强放疗疗效的有前景的策略。其中,钛酸纳米管(TNTs)因其生物相容性和成本效益而受到了广泛关注。本研究旨在从钠钛酸纳米管(NaTNT)合成锌改性钛酸纳米管(ZnTNT),此外还对形成的纳米结构进行表征,并评估它们对GBM细胞(U87和U251)的放射增敏作用。采用水热合成法制备钛酸纳米管,并用多种技术对其进行表征,包括透射电子显微镜(TEM)、能量色散光谱、扫描透射模式、傅里叶变换红外光谱、电感耦合等离子体质谱(ICP-MS)、X射线光电子能谱和zeta电位分析。通过MTT法在健康细胞(Vero)和GBM细胞(U87和U251)中评估细胞毒性,同时通过TEM成像和ICP-MS观察钛酸纳米管的内化情况。使用克隆形成试验评估ZnTNT和NaTNT与5 Gy联合使用时的放射敏感性。使用MCNP6.2代码进行蒙特卡罗模拟,以确定涉及钛酸纳米管簇和细胞的放疗场景下培养基中的沉积剂量。结果表明有无钛酸纳米管的场景之间的剂量沉积值存在差异。该研究表明,ZnTNT会干扰克隆形成完整性,表明其作为GBM治疗有力工具的潜力。