Cascade enzymes within self-assembled hybrid nanogel mimicked neutrophil lysosomes for singlet oxygen elevated cancer therapy

As the first line of innate immune cells to migrate towards tumour tissue, neutrophils, can immediately kill abnormal cells and activate long-term specific adaptive immune responses. Therefore, the enzymes mediated elevation of reactive oxygen species (ROS) bioinspired by neutrophils can be a promising strategy in cancer immunotherapy. Here, we design a core-shell supramolecular hybrid nanogel via the surface phosphatase triggered self-assembly of oligopeptides around iron oxide nanoparticles to simulate productive neutrophil lysosomes. The cascade reaction of superoxide dismutase (SOD) and chloroperoxidase (CPO) within the bioinspired nanogel can convert ROS in tumour tissue to hypochlorous acid (HOCl) and the subsequent singlet oxygen ((1)O(2)) species. Studies on both cells and animals demonstrate successful (1)O(2)-mediated cell/tumour proliferation inhibition, making this enzyme therapy capable for treating tumours without external energy activation.