This work, reported by Fan Wepai from China Pharmaceutical University, Ju Shenghong from Southeast University, Yu Wenying from China Pharmaceutical University, and Tang Longguang from Zhejiang University, presents a highly engineered "in situ self-assembling cell reservoir hydrogel" for precisely manipulating the immune response rhythm after radiotherapy, thereby achieving true multi-stage radio-immunotherapy. The authors ingeniously used red blood cells (RBCs) as functional carriers, loading aCTLA-4 and IL-12, and combining them with the BaO₂/sodium alginate system. This triggered in situ hydrogel self-assembly in the tumor acidic microenvironment.
This system achieves three key mechanisms:
First, BaO₂ decomposes in the acidic tumor microenvironment to produce H₂O₂, which is converted into O₂ under the action of endogenous peroxidase in red blood cells, continuously alleviating tumor hypoxia and enhancing radiotherapy sensitivity;
Second, O₂ generation induces the formation of transient pores in the red blood cell membrane, promoting the rapid release of aCTLA-4, and preferentially relieving the immunosuppression induced by radiotherapy;
Third, as the hydrogel gradually degrades, IL-12 is released slowly, continuously activating T/NK cells, and amplifying IFN-γ-dependent anti-tumor immunity.
Through this time-programmed and space-restricted immune regulation, this hydrogel not only significantly enhances the immunogenic cell death induced by radiotherapy, but also achieves strong tumor clearance, immune memory establishment, and tumor recurrence inhibition in breast cancer and pancreatic cancer models. Overall, this work demonstrates a new idea of integrating material self-assembly, engineered cells, and immune rhythm control in radio-immunotherapy, with clear clinical translation potential. The related research was published in Nature Communications under the title "In situ self-assembled cell reservoir hydrogel for maneuvering multistage radioimmunotherapy".
Original link：https://www.nature.com/articles/s41467-026-68490-5
