Radioactive nano-oxygen generator enhance anti-tumor radio-immunotherapy by regulating tumor microenvironment and reducing proliferation

Oxygen (O-2) is the substance irreplaceable of the body's metabolism, which is not only the primary consumable of life activities, but also provide the input energy for the whole body. Importantly, the O-2 supply will act as an important role in the field of tumor theranostics. Herein, we successfully construct a radioactive nano-oxygen generator (Lu-177-APPs-PEG) with superior properties, which can not only realize a high-performance radioisotope labelling, but also unfreeze the limitation of O-2 dependence of internal radioisotope therapy (IRT). More importantly, such nano-oxygen generator also can effectively enhance the infiltration of cytotoxic T cells (CTLs) in distant tumors and reduce tumor metastasis. Meanwhile, the increase of O-2 in tumor-site can affect the metabolism of tumor cells and regulatory T (Treg) cells to reduce cancer cells proliferation by down-regulating the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and c-Myc. In short, the strategies we designed provide a new idea for the influence of nano-enzymes on tumor metabolism and immunotherapy.

Automated summary

In this study, a radioactive nano-oxygen generator was successfully constructed, which can achieve efficient radioisotope labeling and overcome the limitation of oxygen dependence in internal radioisotope therapy. This nano-oxygen generator can enhance the infiltration of cytotoxic T cells in distant tumors, reduce tumor metastasis, and inhibit cancer cell proliferation by affecting the metabolism of tumor cells and regulatory T cells.