4.3 Article

Tumor microenvironment regulation - enhanced radio - immunotherapy

Journal

BIOMATERIALS ADVANCES
Volume 138, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.bioadv.2022.212867

Keywords

Radiotherapy; Immunotherapy; Tumor microenvironment regulation

Funding

  1. AIST, Japan Society for the Promotion of Science (JSPS, KAKENHI) [22H03964, 17K01399]
  2. Grants-in-Aid for Scientific Research [17K01399] Funding Source: KAKEN

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Radiotherapy (RT) has immune stimulation potency in cancer treatment, but its inhibitory effect on tumor growth and metastasis is limited. This study highlights the potential strategy of using SiO2@MnO2 nanoparticles (SM NPs) to regulate TME and enhance the effectiveness of RT and immunotherapy.
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 SiO2@MnO2 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.

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