Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Rokkodaicho 1-1, Nada-ku, Kobe 657-8501, Japan; Research Facility Center for Science and Technology, Kobe University, Rokkodaicho 1-1, Nada-ku, Kobe 657-8501, Japan.
Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Rokkodaicho 1-1, Nada-ku, Kobe 657-8501, Japan.
Colloids Surf B Biointerfaces. 2021 Feb;198:111451. doi: 10.1016/j.colsurfb.2020.111451. Epub 2020 Nov 7.
Polyacrylic acid-modified titanium peroxide nanoparticles (PAA-TiO NPs) are promising radiosensitizers that enhance the therapeutic effect of X-ray irradiation after local injection into tumors. However, the mechanism for this reaction has remained unclear with the exception of the involvement of hydrogen peroxide (HO), which is released by PAA-TiO NPs to a liquid phase during dispersion. In the present study, a clonogenic assay was used to compare PAA-TiO NPs with free HO molecules to investigate the effect exerted on the radiosensitivity of cancer cells in vitro. A cell-free dialysis method revealed that a portion of the HO adsorbed onto the PAA-TiO NPs during synthesis could be released during a treatment regimen. The HO release lasted for 7 h, which was sufficient for one radiation treatment procedure. For in vitro experiments, cultured human pancreatic cancer cells took up PAA-TiO NPs in 10 min after administration. Interestingly, when the cells were washed with a buffer after treatment with either a PAA-TiO NP or HO solution, the intracellular HO levels remained higher with PAA-TiO NP treatment compared with the HO solution treatment. Furthermore, the effects of subsequent X-ray irradiation corresponded to the intracellular HO levels. These results indicate that PAA-TiO NPs are efficient carriers of HO into cancer cells and thus enhance the radiosensitivity.
聚丙烯酸改性过氧化钛纳米粒子（PAA-TiO NPs）是一种很有前途的放射增敏剂，在局部注射到肿瘤后，可增强 X 射线照射的治疗效果。然而，除了 PAA-TiO NPs 在分散过程中向液相释放过氧化氢（HO）这一反应机制外，这种反应的机制仍不清楚。在本研究中，采用集落形成实验将 PAA-TiO NPs 与游离 HO 分子进行比较，以研究其对体外癌细胞放射敏感性的影响。无细胞透析法表明，在合成过程中吸附在 PAA-TiO NPs 上的一部分 HO 可以在治疗方案中释放。HO 的释放持续 7 小时，足以进行一次放射治疗。在体外实验中，给药 10 分钟后，培养的人胰腺癌细胞即可摄取 PAA-TiO NPs。有趣的是，当用 PAA-TiO NP 或 HO 溶液处理后的细胞用缓冲液洗涤时，与用 HO 溶液处理相比，PAA-TiO NP 处理后细胞内的 HO 水平仍然更高。此外，随后的 X 射线照射的效果与细胞内的 HO 水平相对应。这些结果表明，PAA-TiO NPs 是将 HO 有效递送到癌细胞中的载体，从而增强了放射敏感性。
