Endoplasmic reticulum targeted AIE bioprobe as a highly efficient inducer of immunogenic cell death
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tps://doi.org/10.1007/s11426-020-9846-4
SPECIAL ISSUE: 2020 Emerging Investigator Issue
Endoplasmic reticulum targeted AIE bioprobe as a highly efficient inducer of immunogenic cell death 1†
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Jun Li , Heqi Gao , Ruihua Liu , Chao Chen , Sheng Zeng , Qian Liu & Dan Ding 1
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Key Laboratory of Bioactive Materials Ministry of Education, College of Life Sciences, and State Key Laboratory of Medicinal Chemical 2
Biology, Nankai University, Tianjin 300071, China; Department of Urology, Tianjin First Central Hospital, Tianjin 300192, China
Received July 2, 2020; accepted August 11, 2020; published online August 27, 2020
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 aggregationinduced 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 calreticulin, 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. immunogenic cell death, endoplasmic reticulum oxidative stress, aggregation-induced emission, reactive oxygen species Citation:
Li J, Gao H, Liu R, Chen C, Zeng S, Liu Q, Ding D. Endoplasmic reticulum targeted AIE bioprobe as a highly efficient inducer of immunogenic cell death. Sci China Chem, 2020, 63, https://doi.org/10.1007/s11426-020-9846-4
In recent years, tumor immunotherapy has brought new dawn to patients in the advanced treatment of malignant tumors, considering the approvement of immune checkpoint inhibitors CTLA-4 and PD-1 by the Food and Drug Administration (FDA) for clinical treatment of cancer [1]. Although PD-1/PD-L1 is active in advanced cancers such as melanoma, renal cancer and acute lymphoblastic leukemia, its therapeutic effect in some other tumors, such as triple negative breast cancer, is unsatisfactory with poor immunogenicity [2]. Immunogenic cell death (ICD) has emerged as a new type of cell death for decades, which releases damage-associated molecular patterns (DAMPs) to improve immunogenicity, promoting the identification, antigen uptake and presentation of tumors by antigen-pre†These authors contributed equally to this work. *Corresponding authors (email: [email protected]; [email protected]; [email protected])
senting cells, and thus effectively opens a specific antitumor immune response [3]. During the ICD process, DAMPs can be used as natural adjuvant or danger signals for the immune system to enhance t
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