Titanium oxide nano-radiosensitizers for hydrogen peroxide delivery into cancer cells
Titanium oxide nano-radiosensitizers for hydrogen peroxide delivery into cancer cells
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DOI：
10.1016/j.colsurfb.2020.111451
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发表时间：
2021-02-13
影响因子：
5.8
通讯作者：
Kondo, Akihiko
中科院分区：
文献类型：
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作者：
Morita, Kenta;Nishimura, Yuya;Kondo, Akihiko
聚丙烯酸修饰的过氧化钛纳米颗粒（PAA-TiOx NPs）是一种很有前途的放射增敏剂，其在局部注射到肿瘤中后可增强X射线照射的治疗效果。然而，该反应的机制仍然不清楚，除了过氧化氢（H2 O2）的参与，其在分散期间由PAA-TiOx NP释放到液相。在本研究中，使用克隆形成测定来比较PAA-TiOx NPs与游离H2 O2分子，以研究对体外癌细胞的放射敏感性的影响。无细胞透析方法揭示了在合成期间吸附到PAA-TiOx NP上的一部分H2 O2可以在处理方案期间释放。H2 O2释放持续7 h，足以进行一次放射治疗程序。对于体外实验，培养的人胰腺癌细胞在施用后10分钟内摄取PAA-TiOx NP。有趣的是，当用PAA-TiOx NP或H2 O2溶液处理后用缓冲液洗涤细胞时，与H2 O2溶液处理相比，用PAA-TiOx NP处理的细胞内H2 O2水平保持更高。此外，随后X射线照射的影响与细胞内H2 O2水平相对应。这些结果表明，PAA-TiOx纳米颗粒是H2 O2进入癌细胞的有效载体，从而增强了放射敏感性。
Polyacrylic acid-modified titanium peroxide nanoparticles (PAA-TiOx 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 (H2O2), which is released by PAA-TiOx NPs to a liquid phase during dispersion. In the present study, a clonogenic assay was used to compare PAA-TiOx NPs with free H2O2 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 H2O2 adsorbed onto the PAA-TiOx NPs during synthesis could be released during a treatment regimen. The H2O2 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-TiOx NPs in 10 min after administration. Interestingly, when the cells were washed with a buffer after treatment with either a PAA-TiOx NP or H2O2 solution, the intracellular H2O2 levels remained higher with PAA-TiOx NP treatment compared with the H2O2 solution treatment. Furthermore, the effects of subsequent X-ray irradiation corresponded to the intracellular H2O2 levels. These results indicate that PAA-TiOx NPs are efficient carriers of H2O2 into cancer cells and thus enhance the radiosensitivity.