Liu Zimo, Zhou Xuefei, Li Qi, Shen Youqing, Zhou Tianhua, Liu Xiangrui
Department of Pharmacology and Department of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
Acta Pharm Sin B. 2023 Jan;13(1):327-343. doi: 10.1016/j.apsb.2022.05.010. Epub 2022 May 13.
Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical applications. However, administered nanoparticles are rapidly sequestered and cleared by cells of the mononuclear phagocyte system (MPS). In this study, we developed a biomimetic nanosystem that is able to efficiently escape MPS and target tumor tissues. The fabricated nanoparticles (TM-CQ/NPs) were coated with fibroblast cell membrane expressing tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). Coating with this functionalized membrane reduced the endocytosis of nanoparticles by macrophages, but increased the nanoparticle uptake in tumor cells. Importantly, this membrane coating specifically induced tumor cell apoptosis the interaction of TRAIL and its cognate death receptors. Meanwhile, the encapsulated chloroquine (CQ) further suppressed the uptake of nanoparticles by macrophages, and synergized with TRAIL to induce tumor cell apoptosis. The vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS challenge for cancer therapy. Together, our TM-CQ/NPs nanosystem provides a feasible approach to precisely target tumor tissues and improve anticancer efficacy.
抗癌纳米药物在血流中的延长循环对其临床应用至关重要。然而，所施用的纳米颗粒会迅速被单核吞噬细胞系统（MPS）的细胞隔离和清除。在本研究中，我们开发了一种能够有效逃离MPS并靶向肿瘤组织的仿生纳米系统。制备的纳米颗粒（TM-CQ/NPs）用表达肿瘤坏死因子（TNF）相关凋亡诱导配体（TRAIL）的成纤维细胞膜包被。用这种功能化膜包被可减少巨噬细胞对纳米颗粒的内吞作用，但增加肿瘤细胞对纳米颗粒的摄取。重要的是，这种膜包被通过TRAIL与其同源死亡受体的相互作用特异性诱导肿瘤细胞凋亡。同时，封装的氯喹（CQ）进一步抑制巨噬细胞对纳米颗粒的摄取，并与TRAIL协同诱导肿瘤细胞凋亡。在两种小鼠肿瘤模型中的强大抗肿瘤功效证实了我们的纳米系统是应对癌症治疗中MPS挑战的有效方法。总之，我们的TM-CQ/NPs纳米系统提供了一种精确靶向肿瘤组织并提高抗癌功效的可行方法。
