Institute of Nature and Environmental Technology, Kanazawa University, Kanazawa 920-1192, Japan.
Ultrason Sonochem. 2012 May;19(3):607-14. doi: 10.1016/j.ultsonch.2011.09.009. Epub 2011 Oct 4.
Our previous study suggested new sonodynamic therapy for cancer cells based on the delivery of titanium dioxide (TiO(2)) nanoparticles (NPs) modified with a protein specifically recognizing target cells and subsequent generation of hydroxyl radicals from TiO(2) NPs activated by external ultrasound irradiation (called TiO(2)/US treatment). The present study first examined the uptake behavior of TiO(2) NPs modified with pre-S1/S2 (model protein-recognizing hepatocytes) by HepG2 cells for 24h. It took 6h for sufficient uptake of the TiO(2) NPs by the cells. Next, the effect of the TiO(2)/US treatment on HepG2 cell growth was examined for 96 h after the 1 MHz ultrasound was irradiated (0.1 W/cm(2), 30s) to the cells which incorporated the TiO(2) NPs. Apoptosis was observed at 6h after the TiO(2)/US treatment. Although no apparent cell-injury was observed until 24h after the treatment, the viable cell concentration had deteriorated to 46% of the control at 96 h. Finally, the TiO(2)/US treatment was applied to a mouse xenograft model. The pre-S1/S2-immobilized TiO(2) (0.1mg) was directly injected into tumors, followed by 1 MHz ultrasound irradiation at 1.0 W/cm(2) for 60s. As a result of the treatment repeated five times within 13 days, tumor growth could be hampered up to 28 days compared with the control conditions.
我们之前的研究提出了一种新的基于二氧化钛（TiO2）纳米颗粒（NPs）的声动力学疗法，该 NPs 经过修饰可特异性识别靶细胞的蛋白质，随后通过外部超声辐射激活 TiO2 NPs 产生羟基自由基（称为 TiO2/US 处理）。本研究首先考察了 HepG2 细胞在 24 小时内对预 S1/S2（识别肝细胞的模型蛋白）修饰的 TiO2 NPs 的摄取行为。细胞摄取 TiO2 NPs 需要 6 小时。接下来，在将 TiO2 NPs 整合到细胞中后，用 1MHz 超声（0.1W/cm2，30s）照射细胞 96 小时，考察 TiO2/US 处理对 HepG2 细胞生长的影响。在 TiO2/US 处理后 6 小时观察到细胞凋亡。虽然在处理后 24 小时内没有观察到明显的细胞损伤，但在 96 小时时活细胞浓度已恶化至对照组的 46%。最后，将 TiO2/US 处理应用于小鼠异种移植模型。将预 S1/S2 固定化的 TiO2（0.1mg）直接注入肿瘤中，然后用 1MHz 超声在 1.0W/cm2 下照射 60s。在 13 天内重复进行 5 次治疗后，与对照组相比，肿瘤生长可被抑制长达 28 天。
