Graduate School of Creative Science and Engineering, Waseda University, 3-4-1 Shin-Okubo, Shinjuku-ku, Tokyo 169-8555, Japan.
Health and Medical Research Institute, Department of Life Science and Biotechnology, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Biomater Adv. 2022 Jul;138:212867. doi: 10.1016/j.bioadv.2022.212867. Epub 2022 May 18.
Radiotherapy (RT) is frequently utilized for cancer treatment in clinical practice and has been proved to have immune stimulation potency in recent years. However, its inhibitory effect on tumor growth, especially on tumor metastasis, is still limited by many factors, including the complex tumor microenvironment (TME). Therefore, the TME - regulating SiO@MnO nanoparticles (SM NPs) were prepared and applied to the combination of RT and immunotherapy. In a bilateral animal model, SM NPs not only enhanced the inhibitory effect of RT on primary tumor growth, but also strengthened the abscopal effect to inhibit the growth of distant untreated tumors. As for the distant untreated tumor, 40% of mice showed complete inhibition of tumor growth and 40% showed a suppressed tumor growth. Moreover, SM NPs showed modulation functions for TME through inducing the increase in intracellular levels of oxygen and reactive oxygen species after their reaction with hydrogen peroxide and the main antioxidative agent glutathione in TME. Lastly, SM NPs also effectively induced the increase in the amounts of cytokines secreted by macrophage - like cells, indicating modulation functions for immune responses. This work highlighted a potential strategy of simultaneously inhibiting tumor growth and metastasis through the regulation of TME and immune responses by SM NPs - enhanced radio - immunotherapy.
放射治疗（RT）在临床实践中常用于癌症治疗，近年来已被证明具有免疫刺激作用。然而，其对肿瘤生长的抑制作用，特别是对肿瘤转移的抑制作用，仍受到许多因素的限制，包括复杂的肿瘤微环境（TME）。因此，制备了 TME 调节 SiO@MnO 纳米颗粒（SM NPs），并将其应用于 RT 和免疫治疗的联合治疗。在双侧动物模型中，SM NPs 不仅增强了 RT 对原发性肿瘤生长的抑制作用，而且还增强了远隔未治疗肿瘤的旁观者效应抑制作用。对于远隔未治疗的肿瘤，有 40%的小鼠表现出肿瘤完全抑制，40%的小鼠表现出肿瘤生长受到抑制。此外，SM NPs 通过与 TME 中的过氧化氢和主要抗氧化剂谷胱甘肽反应，诱导细胞内氧气和活性氧水平的增加，以及调节 TME，从而发挥调节功能。最后，SM NPs 还能有效地诱导巨噬细胞样细胞分泌细胞因子的增加，表明对免疫反应具有调节功能。这项工作强调了一种通过 SM NPs 增强的放射免疫治疗来调节 TME 和免疫反应，从而同时抑制肿瘤生长和转移的潜在策略。
