A neutrophil mimicking metal-porphyrin-based nanodevice loaded with porcine pancreatic elastase for cancer therapy

Tingting Cui; Yu Zhang; Geng Qin; Yue Wei; Jie Yang; Ying Huang; Jinsong Ren; Xiaogang Qu

doi:10.1038/s41467-023-37580-z

A neutrophil mimicking metal-porphyrin-based nanodevice loaded with porcine pancreatic elastase for cancer therapy

Nat Commun. 2023 Apr 8;14(1):1974. doi: 10.1038/s41467-023-37580-z.

Authors

Tingting Cui^{1

2}, Yu Zhang^{1

2}, Geng Qin^{1

2}, Yue Wei^{1

2}, Jie Yang^{1

2}, Ying Huang^{1

2}, Jinsong Ren^{1

2}, Xiaogang Qu^{3

4}

Affiliations

¹ State Key Laboratory of Rare Earth Resource Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, P. R. China.
² School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China.
³ State Key Laboratory of Rare Earth Resource Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, P. R. China. xqu@ciac.ac.cn.
⁴ School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China. xqu@ciac.ac.cn.

Abstract

Precise discrimination and eradication of cancer cells by immune cells independent of antigen recognition is promising for solid tumor therapeutics, yet remains a tremendous challenge. Inspired by neutrophils, here we design and construct a tumor discrimination nanodevice based on the differential histone H1 isoform expression. In this nanodevice, neutrophil membrane camouflage and glutathione (GSH)-unlocking effect on Fe-porphyrin metal-organic framework structure ensures selectivity to cancer cells. The released porcine pancreatic elastase (PPE) simulates neutrophils' action to induce histone H1 release-dependent selective cancer cell killing. Meanwhile, nuclear localization signal (NLS) peptide-tagged porphyrin (porphyrin-NLS) acts as in-situ singlet oxygen (¹O₂) generator to amplify histone H1 nucleo-cytoplasmic translocation by inducing DNA double-strand breaks (DSBs) under laser irradiation, further promoting elimination of cancer cells. The overexpressed histone H1 isoform in cancer cells improves selectivity of our nanodevice to cancer cells. In vivo studies demonstrate that our design can not only inhibit primary tumor growth, but also induce adaptive T-cell response-mediated abscopal effect to against distal tumors.

Publication types

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

MeSH terms

Animals
Glutathione / metabolism
Histones
Metals / metabolism
Neoplasms*
Neutrophils / metabolism
Pancreatic Elastase* / metabolism
Protein Isoforms / metabolism
Swine

Substances

Pancreatic Elastase
Histones
Glutathione
Protein Isoforms
Metals