1. Academic Validation
  2. A nanodrug combining CD47 and sonodynamic therapy efficiently inhibits osteosarcoma deterioration

A nanodrug combining CD47 and sonodynamic therapy efficiently inhibits osteosarcoma deterioration

  • J Control Release. 2023 Feb 2;355:68-84. doi: 10.1016/j.jconrel.2023.01.038.
Ming Gong 1 Yufeng Huang 1 Huixiong Feng 1 Jiaming Lin 1 Anfei Huang 1 Jinxin Hu 1 Qinglian Tang 1 Xiaojun Zhu 1 Shisong Han 2 Jinchang Lu 3 Jin Wang 4
Affiliations

Affiliations

  • 1 Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China; State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, PR China.
  • 2 Zhuhai Institute of Translational Medicine, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai 519000, PR China. Electronic address: whuhss@whu.edu.cn.
  • 3 Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China; State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, PR China. Electronic address: lujc1@sysucc.org.cn.
  • 4 Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China; State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, PR China. Electronic address: wangjinr@sysucc.org.cn.
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.

Keywords

CD47 immune checkpoint; Nanodrug; Osteosarcoma; Sonodynamic therapy; Tumor associated macrophages.

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