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Journal of Controlled Release

Journal of Controlled Release

IF: 10.5
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A nanodrug combining CD47 and sonodynamic therapy efficiently inhibits osteosarcoma deterioration.

Published:1 March 2023 DOI: 10.1016/j.jconrel.2023.01.038 PMID: 36682726
Ming Gong , Yufeng Huang , Huixiong Feng , Jiaming Lin , Anfei Huang , Jinxin Hu , Qinglian Tang , Xiaojun Zhu , Shisong Han , Jinchang Lu , Jin Wang

Abstract

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.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
RRX-001 925206-65-1 C5H6BrN3O5 115 suppliers $19.00-$3450.00
RRX-001 925206-65-1 C5H6BrN3O5 115 suppliers $19.00-$3450.00
RRX-001 925206-65-1 C5H6BrN3O5 115 suppliers $19.00-$3450.00
RRX-001 925206-65-1 C5H6BrN3O5 115 suppliers $19.00-$3450.00

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