声动力疗法
CD47型
癌症研究
肿瘤微环境
巨噬细胞极化
骨肉瘤
细胞凋亡
巨噬细胞
化学
肿瘤相关巨噬细胞
吞噬作用
体内
医学
免疫学
体外
生物
生物技术
生物化学
肿瘤细胞
作者
Ming Gong,Yufeng Huang,Huixiong Feng,Jiamao Lin,Anfei Huang,Jinxin Hu,Qinglian Tang,Xuejun Zhu,Shisong Han,Jinchang Lu,Jin Wang
标识
DOI:10.1016/j.jconrel.2023.01.038
摘要
Treatments for osteosarcoma (OS) with pulmonary metastases reach a bottleneck with a survival rate of 10-20%. The suppressive tumor associated macrophages(TAMs) and CD47 over-expression greatly lead to the treatment failure. Sonodynamic therapy (SDT) can generate ROS with deep tumor penetration to induce tumor cell apoptosis, which is reported to further induce M1 macrophage polarization. CD47 inhibition combined with SDT to synergistically modulate TAMs may induce superior effects for OS treatment. In this work, for the first time, a biomimetic nanodrug named MPIRx was deveploped by loading IR780 (a sonosensitizer) and RRx-001 (a CD47 inhibitor) in PEG-PCL nanomicelles and then coating with OS cell membranes. After ultrasound activation, the nanodrug significantly inhibited OS proliferation and migration, induced apoptosis and immunogenic cell death in OS cells. Furthermore, MPIRx could guide macrophage migrating towards tumor cells and promote M1-type polarization while increasing the phagocytosis activity of macrophages on OS cells. Ultimately, MPIRx showed good tumor accumulation in vivo and successfully inhibited subcutaneous OS and orthotopic tumor with deterioration of pulmonary metastasis. Overall, by creating a local oxidative microenvironment and modulating the TAMs/CD47 in tumor tissue, the MPIRx nanodrug presents a novel strategy for macrophage-related immunotherapy to successfully eliminate OS and inhibit the intractable pulmonary metastasis.
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