Multifunctional carbon monoxide nanogenerator as immunogenic cell death drugs with enhanced antitumor immunity and antimetastatic effect.

Abstract

The limited effect of immune checkpoint blockade (ICB) immunotherapy is subjected to the immuno-suppressive tumor microenvironment (TME). It is still a challenge to reverse the immune-suppressive state in clinical cancer therapy. Immunogenic cell death (ICD) is a way for inducing the therapeutical tumor immune system. In this work, carbon monoxide (CO) gas therapy is used to boost antitumor immunity for tumor control, metastasis and recurrence prevention. Briefly, CO₂-g-C₃N₄-Au@ZIF-8@F127 (CCAZF) is proposed to integrate gas therapy and immunotherapy into a photocatalytic nanogenerator for overcoming the limitations of monotherapy. CCAZF exhibits a highly effective light-controllable release behavior of CO, which gradually aggravates the oxidative stress in tumor cells to induce ICD. With the induction of ICD, CO therapy enhances immune responses and enables efficient immune cells activated. When combined with ICB, CCAZF displays an enhanced immune effect, which mediates the regression of primary and distal tumors. This strategy of in-situ photocatalytic CO therapy furthest avoids the toxicity from CO leakage and provides a new method to design novel ICD inducers.