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

• Published in: Nature communications Vol. 10; no. 1; p. 240
• Main Authors: Wu, Qing, He, Zhigang, Wang, Xia, Zhang, Qi, Wei, Qingcong, Ma, Sunqiang, Ma, Cheng, Li, Jiyu, Wang, Qigang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.01.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13/2; 59/5; 631/67/1059; 631/67/327; 639/301/923/1027; 639/925/350/354; Adaptive immunity; Animals; Cancer; Cancer immunotherapy; Cancer therapies; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - therapy; Cascade chemical reactions; Cell migration; Cell proliferation; Chloride Peroxidase - chemistry; Chloride Peroxidase - metabolism; Enzymes; Female; Ferrosoferric Oxide - chemistry; Hep G2 Cells; Humanities and Social Sciences; Humans; Hydrogels - chemistry; Hydrogels - therapeutic use; Hypochlorous acid; Hypochlorous Acid - metabolism; Immune response; Immune system; Immunotherapy; Iron oxides; Leukocytes (neutrophilic); Liver - pathology; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Liver Neoplasms - therapy; Lysosomes; Lysosomes - immunology; Lysosomes - metabolism; Male; Metal Nanoparticles - chemistry; Metal Nanoparticles - therapeutic use; Metal Nanoparticles - ultrastructure; Mice; Mice, Inbred NOD; Mice, Nude; Mice, SCID; Microscopy, Electron, Scanning; multidisciplinary; Nanomedicine - methods; Nanoparticles; Neutrophils; Neutrophils - immunology; Neutrophils - metabolism; Oligopeptides; Oxygen; Reactive oxygen species; Science; Science (multidisciplinary); Self-assembly; Singlet oxygen; Singlet Oxygen - metabolism; Superoxide dismutase; Superoxide Dismutase - chemistry; Superoxide Dismutase - metabolism; Therapy; Tissues; Treatment Outcome; Tumors; Xenograft Model Antitumor Assays
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-08234-2

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. Enzymatic reactions caused by neutrophils can cause the elevation of reactive oxygen species (ROS) in tumour tissue, Here, the authors, inspired by the neutrophils, design and test a synthetic cascade reaction which turns ROS into singlet oxygen and demonstrate the application of the designed nanoparticle