Inducing Endoplasmic Reticulum Stress to Expose Immunogens: A DNA Tetrahedron Nanoregulator for Enhanced Immunotherapy,Advanced Functional Materials

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Inducing Endoplasmic Reticulum Stress to Expose Immunogens: A DNA Tetrahedron Nanoregulator for Enhanced Immunotherapy
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2020-09-16 , DOI: 10.1002/adfm.202000532
Yanhua Li ₁ , Xia Zhang ₁ , Xiuyan Wan ₁ , Xiaohan Liu ₁ , Wei Pan ₁ , Na Li ₁ , Bo Tang ₁

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Immunogenic cell death (ICD) is an important modulation type for stimulating anticancer immune responses and amplifying immunotherapy efficacy. When ICD occurs, endoplasmic reticulum (ER) stress plays a vital role for exposing immunogens. Herein, a functionalized DNA tetrahedron nanoregulator to specifically trigger ER stress for enhancing cancer immunotherapy is designed. The nanoregulator can target ER organelles by binding to the sulfonamide receptor of cancer cells. Then glucose depletion and reactive oxygen species generation cause a strong ER stress response to induce ICD to expose tumor immunogens. Thereafter, the dendritic cell (DC) maturation is promoted, and T cell proliferation and infiltration are stimulated to advance cancer immunotherapy. Combined with immune checkpoint inhibitor (α‐PD‐1), the ER stress triggered nanoregulator exhibits significant suppression for breast cancer and melanoma.

中文翻译：

诱导内质网应激暴露免疫原：增强免疫治疗的DNA四面体纳米调节剂。

免疫原性细胞死亡（ICD）是刺激抗癌免疫反应和增强免疫治疗功效的重要调节类型。当发生ICD时，内质网（ER）应激对于暴露免疫原起着至关重要的作用。本文中，设计了一种功能化的DNA四面体纳米调节剂，以特异性触发ER应激以增强癌症免疫疗法。纳米调节剂可通过与癌细胞的磺酰胺受体结合而靶向ER细胞器。然后，葡萄糖的消耗和活性氧的产生会引起强烈的内质网应激反应，从而诱导ICD暴露出肿瘤免疫原。此后，促进树突状细胞（DC）的成熟，并刺激T细胞增殖和浸润以推进癌症免疫治疗。结合免疫检查点抑制剂（α‐PD‐1），

更新日期：2020-11-25

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