由于其固有优势，小干扰RNA（siRNA）在恶性肿瘤治疗中的潜力引起了越来越多的关注。然而，它们在体内胞质传递的治疗效果强烈依赖于具有良好细胞渗透性和组织相容性的传递载体的效率。在这里，我们通过仿生方式构建了一种以巨噬细胞膜伪装的多阳离子载体，它是通过硒醚键由内源的精胺单体缩合而成的。发展的特洛伊木马式传递载体具有较理想的siPDL1压缩效能，以及由肿瘤细胞中的氧化还原微环境触发的顺序降解引发的细胞质释放特性。此外，光敏剂的联合载荷可以在光辐照作用下介导光动力疗法，并伴随活性氧（ROS）的产生，从而加速载体的降解以及货物的释放，同时通过诱导原位免疫细胞死亡来增强PDL1阻断介导的免疫疗法。此外，同时传递的siPDL1减弱了ROS诱导的免疫抑制性PDL1表达的增加，从而在移植乳腺癌小鼠模型中以“自身协同”方式有效引发强大的抗肿瘤免疫反应。该文章受版权保护。版权所有。

The potential of small interfering RNAs (siRNAs) in the treatment of malignant tumors has attracted increasing attention due to their inherent advantages. However, their therapeutic performance strongly depends on the efficiency of their cytoplasmic delivery in vivo by the delivery vehicle with good cellular permeability and histocompatibility. Herein, a polycationic carrier camouflaged with macrophage membrane was constructed biomimetically, which was condensed from endogenous spermine monomers through diselenide bonds. The developed Trojan horse delivery vehicle has desirable compression efficacy for siPDL1 as well as intracytoplasmic release properties derived from its sequential degradation triggered by redox microenvironment in tumor cells. Further, the co-loading of photosensitizer could mediate PDT accompanied by the generation of reactive oxygen species (ROS) upon light irradiation applied, which accelerated the degradation of the carrier as well as the release of cargoes while enhancing the PDL1 blockage-mediated immunotherapy by inducing in situ immunogenic cell death. Moreover, the synchronously delivered siPDL1 attenuated the ROS-induced increase in immunosuppressive PDL1 expression, thereby effectively eliciting a robust antitumor immune response with a "self-synergistic" manner in the xenograft breast cancer mouse model. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.