Medicine and Health

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

T. Cui, Y. Zhang, et al.

Discover an innovative tumor discrimination nanodevice inspired by neutrophils, designed for precise cancer cell elimination regardless of antigen recognition. This groundbreaking research by Tingting Cui, Yu Zhang, Geng Qin, Yue Wei, Jie Yang, Ying Huang, Jinsong Ren, and Xiaogang Qu showcases a selective and effective approach to combating solid tumors, demonstrating promising in vivo results in tumor growth inhibition and adaptive immune response activation.

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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 (<sup>1</sup>O<sub>2</sub>) 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.

Publisher

Nature Communications

Published On

Apr 08, 2023

Authors

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

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