Reversing the Immunosuppressive Microenvironment with Reduced Redox Level by Microwave-Chemo-Immunostimulant Ce-Mn MOF for Improved Immunotherapy

Backgrounds: : Reversing the immunosuppressive microenvironment (TME) in the tumor is widely deemed to be an effective strategy to improve immune therapy. In particular, the redox balance in TME needs to be well controlled due to its critical role in mediating the functions of various cells, including cancer cells and immune-suppressive cells. Here, we propose an efficient strategy to reshape the redox homeostasis to reverse immunosuppressive TME. Results Specifically, we developed a microwave-chemo-immunostimulant CMMCP to promote the generation of the tumor-infiltration T cells by simultaneously reducing the reactive oxygen species (ROS) and glutathione (GSH) and improving the oxygen levels in TME. The CMMCP was designed by loading chemotherapy drugs cisplatin into the bimetallic Ce-Mn MOF nanoparticles coated with polydopamine. The Ce-Mn MOF nanoparticles can effectively improve the catalytic decomposition of ROS into O 2 under microwave irradiation, resulting in the overcome hypoxia and limited ROS generation. Besides, the activity of intracellular GSH in TME was reduced by the redox reaction with Mn 2+ of Ce-Mn MOF nanoparticles. The reprogrammed TME not only boosts the immunogenic cell death (ICD) induced by cisplatin and microwave hyperthermia but also gives rise to the polarization of pro-tumor M2-type macrophages to the anti-tumor M1-type ones. Conclusion Our in vivo experimental results demonstrate that the microwave-chemo-immunostimulant CMMCP significantly enhances the T cells infiltration and thus improves the antitumor effect. This study presents an easy, safe, and effective strategy for a whole-body antitumor effect after local treatment.