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Endoplasmic reticulum targeted AIE bioprobe as a highly efficient inducer of immunogenic cell death

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Abstract

Focused oxidative stress of the specific organelles (e.g., endoplasmic reticulum (ER) and mitochondrion) of cancer cells can boost the immunogenic cell death (ICD) effect for cancer immunotherapy. Herein, an ER-targeted bioprobe with aggregation-induced emission (AIE) characteristics (TPE-PR-FFKDEL) was rationally designed and synthesized by integrating a new AIE photosensitizer with ER targeting peptide, which has been demonstrated to be able to efficiently induce ER oxidative stress to evoke ICD. Compared with the photosensitizer hypericin that is well-known as an ER-targeted ICD inducer, TPE-PR-FFKDEL can lead to more robust emission of immunostimulatory damage-associated molecular patterns such as surface-exposed cal-reticulin, ATP secretion, and high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP 70) expression. Furthermore, a range of immune responses are activated to protect mice from the attack of cancer cells in vivo.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (51873092, 51961160730), the National Key R&D Program of China (Intergovernmental Cooperation Project, 2017YFE0132200), Tianjin Science Fund for Distinguished Young Scholars (19JCJQJC61200) and the Fundamental Research Funds for the Central Universities, Nankai University.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Bioactive Materials Ministry of Education, College of Life Sciences, and State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China

    Jun Li, Heqi Gao, Ruihua Liu, Chao Chen & Dan Ding

  2. Department of Urology, Tianjin First Central Hospital, Tianjin, 300192, China

    Sheng Zeng & Qian Liu

Authors
  1. Jun Li
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  2. Heqi Gao
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  3. Ruihua Liu
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  4. Chao Chen
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  5. Sheng Zeng
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  6. Qian Liu
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  7. Dan Ding
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Correspondence to Ruihua Liu, Qian Liu or Dan Ding.

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The supporting information is available online at http://chem.scichina.com and http://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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Li, J., Gao, H., Liu, R. et al. Endoplasmic reticulum targeted AIE bioprobe as a highly efficient inducer of immunogenic cell death. Sci. China Chem. 63, 1428–1434 (2020). https://doi.org/10.1007/s11426-020-9846-4

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  • DOI: https://doi.org/10.1007/s11426-020-9846-4

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