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

Oxygen (O2) 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 O2 supply will act as an important role in the field of tumor theranostics. Herein, we successfully construct a radioactive nano-oxygen generator (177Lu-APPs-PEG) with superior properties, which can not only realize a high-performance radioisotope labelling, but also unfreeze the limitation of O2 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 O2 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-1α (HIF-1α) and c-Myc. In short, the strategies we designed provide a new idea for the influence of nano-enzymes on tumor metabolism and immunotherapy.