The recent years have witnessed the blooming of
cancer immunotherapy, as well as their combinational use together with other existing
cancer treatment techniques including
radiotherapy. However,
hypoxia is one of several causes of the immunosuppressive tumor microenvironment (TME). Herein, we develop an innovative strategy to relieve tumor hypoxia by delivering exogenous H2O2 into
tumors and the subsequent
catalase-triggered H2O2 decomposition. In our experiment, H2O2 and
catalase are separately loaded within stealthy
liposomes. After intravenous (iv) preinjection of CAT@
liposome, another dose of H2O2@
liposome is injected 4 h later. The sustainably released H2O2 could be decomposed by CAT@
liposome, resulting in a long lasting effect in
tumor oxygenation enhancement. As the result, the combination treatment by CAT@
liposome plus H2O2@
liposome offers remarkably enhanced
therapeutic effects in
cancer radiotherapy as observed in a mouse
tumor model as well as a more clinically relevant patient-derived xenograft
tumor model. Moreover, the relieved tumor hypoxia would reverse the immunosuppressive TME to favor antitumor immunities, further enhancing the combined radio-
immunotherapy with
cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade. This work presents a simple yet effective strategy to promote
tumor oxygenation via sequential delivering
catalase and exogenous H2O2 into
tumors using well-established liposomal carriers, showing great potential for clinical translation in radio-
immunotherapy of
cancer.