背景：诱导免疫原性细胞死亡（ICD）是增强免疫检查点阻断（ICB）治疗免疫反应的一种有前途的策略，但缺乏简单有效的平台来整合ICD和ICB治疗限制了它们的临床应用。方法：在这里，我们开发了程序性细胞死亡蛋白 1 (PD1) 过表达的基因工程纳米囊泡 (NVs) 包被的姜黄素 (Cur) 负载的聚乳酸-聚聚乙醇酸纳米粒子 (PD1@Cur-PLGA)，以整合ICD和ICB治疗以增强肿瘤免疫治疗。结果：基因工程NVs大大增强了纳米颗粒的肿瘤靶向性，NVs上的PD1显着阻断了PD1/PDL1信号通路并刺激了抗肿瘤免疫反应。同时，递送的Cur通过抑制NF-κB磷酸化和Bcl-2蛋白表达并激活caspase和Bax凋亡信号传导，成功诱导肿瘤细胞凋亡并激活ICD。通过协同Cur的ICD效应和基因工程NV的PD1/PDL1轴阻断功能，PD1@Cur-PLGA增强了肿瘤组织中成熟树突状细胞和CD8 T细胞的瘤内浸润率，从而显着抑制肿瘤生长乳腺癌和前列腺肿瘤小鼠模型。结论：这种基于基因工程 NV 的 ICD 和 ICB 协同疗法为增强癌症免疫治疗提供了一种低成本、安全且有效的策略。© 作者。

Background: Inducing immunogenic cell death (ICD) is a promising strategy to enhance immune responses for immune checkpoint blockade (ICB) therapy, but the lack of a simple and effective platform to integrate ICD and ICB therapy limits their clinical application. Methods: Here, we developed programmed cell death protein 1 (PD1)-overexpressing genetically engineered nanovesicles (NVs)-coated curcumin (Cur)-loaded poly (lactic-co-poly-polyglycolic acid) nanoparticles (PD1@Cur-PLGA) to integrate ICD and ICB therapy for enhancing tumor immunotherapy. Results: Genetically engineered NVs greatly enhanced the tumor targeting of nanoparticles, and the PD1 on NVs dramatically blocked the PD1/PDL1 signaling pathway and stimulated antitumor immune responses. Meanwhile, the delivered Cur successfully induced tumor cell apoptosis and activated ICD by inhibiting NF-κB phosphorylation and Bcl-2 protein expression and activating caspase and Bax apoptotic signaling. By synergizing the ICD effect of Cur and the PD1/PDL1 axis blocking function of genetically engineered NVs, the PD1@Cur-PLGA enhanced the intratumoral infiltration rate of mature dendritic cells and CD8+ T cells in tumor tissues, resulting in significantly inhibiting tumor growth in breast and prostate tumor-bearing mouse models. Conclusion: This synergistic ICD and ICB therapy based on genetically engineered NVs provides a low-cost, safe, and effective strategy to enhance cancer immunotherapy.© The author(s).