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 and Xiaogang Qu ()
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Tingting Cui: Chinese Academy of Sciences
Yu Zhang: Chinese Academy of Sciences
Geng Qin: Chinese Academy of Sciences
Yue Wei: Chinese Academy of Sciences
Jie Yang: Chinese Academy of Sciences
Ying Huang: Chinese Academy of Sciences
Jinsong Ren: Chinese Academy of Sciences
Xiaogang Qu: Chinese Academy of Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-37580-z

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