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

Qing Wu; Zhigang He; Xia Wang; Qi Zhang; Qingcong Wei; Sunqiang Ma; Cheng Ma; Jiyu Li; Qigang Wang

doi:10.1038/s41467-018-08234-2

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

Nat Commun. 2019 Jan 16;10(1):240. doi: 10.1038/s41467-018-08234-2.

Authors

Qing Wu^{1

2}, Zhigang He¹, Xia Wang³, Qi Zhang¹, Qingcong Wei¹, Sunqiang Ma¹, Cheng Ma¹, Jiyu Li⁴, Qigang Wang⁵

Affiliations

¹ School of Chemical Science and Engineering, Shanghai Tenth People's Hospital & Putuo District People's Hospital, Tongji University, Siping Road 1239, Shanghai, 200092, China.
² State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Science, 865 Changning Road, Shanghai, 200050, China.
³ School of Chemical Science and Engineering, Shanghai Tenth People's Hospital & Putuo District People's Hospital, Tongji University, Siping Road 1239, Shanghai, 200092, China. 15174@tongji.edu.cn.
⁴ School of Chemical Science and Engineering, Shanghai Tenth People's Hospital & Putuo District People's Hospital, Tongji University, Siping Road 1239, Shanghai, 200092, China. lijiyu@tongji.edu.cn.
⁵ School of Chemical Science and Engineering, Shanghai Tenth People's Hospital & Putuo District People's Hospital, Tongji University, Siping Road 1239, Shanghai, 200092, China. wangqg66@tongji.edu.cn.

Abstract

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 (¹O₂) species. Studies on both cells and animals demonstrate successful ¹O₂-mediated cell/tumour proliferation inhibition, making this enzyme therapy capable for treating tumours without external energy activation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma, Hepatocellular / immunology
Carcinoma, Hepatocellular / mortality
Carcinoma, Hepatocellular / pathology
Carcinoma, Hepatocellular / therapy*
Chloride Peroxidase / chemistry
Chloride Peroxidase / metabolism
Female
Ferrosoferric Oxide / chemistry
Hep G2 Cells
Humans
Hydrogels / chemistry
Hydrogels / therapeutic use*
Hypochlorous Acid / metabolism
Liver / pathology
Liver Neoplasms / mortality
Liver Neoplasms / pathology
Liver Neoplasms / therapy*
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
Nanomedicine / methods*
Neutrophils / immunology
Neutrophils / metabolism
Singlet Oxygen / metabolism*
Superoxide Dismutase / chemistry
Superoxide Dismutase / metabolism
Treatment Outcome
Xenograft Model Antitumor Assays

Substances

Hydrogels
Singlet Oxygen
Hypochlorous Acid
Chloride Peroxidase
Superoxide Dismutase
Ferrosoferric Oxide