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

Abstract

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.