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Updated: Jul 18, 2025
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Aspect ratio-dependent dual-regulation of the tumor immune microenvironment against osteosarcoma by hydroxyapatite
Hongfeng Wu1, Ruiqi Wang2, Shu Li3
1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China; College of Biomedical Engineering, Sichuan University, Chengdu 610064, China; Medical School, Kunming University of Science and Technology, Kunming 650500, China.
Abstract:
Accumulating studies demonstrated that hydroxyapatite nanoparticles (HANPs) showed a selective anti-tumor effect, making them a good candidate for osteosarcoma (OS) treatment. However, the capacity of HANPs with different aspect ratios to regulate tumor immune microenvironment (TIM) was scarcely reported before. To explore it, the three HANPs with aspect ratios from 1.86 to 6.25 were prepared by wet chemical method. After a 24 or 72 h-exposure of OS UMR106 cells or macrophages to the nanoparticles, the tumor cells exhibited immunogenic cell death (ICD) indicated by the increased production of calreticulin (CRT), adenosine triphosphate (ATP) and high mobility group box 1 (HMGB1), and macrophages were activated with the release of pro-inflammatory cytokines. Next, the beneficial crosstalk between tumor cells and macrophages generated in the presence of HANPs for improved anti-tumor immunity activation. In the OS-bearing cognate rat model, HANPs inhibited OS growth, which was positively correlated with CRT and HMGB1 expression, and macrophage polarization in the tumor tissues. Additionally, HANPs promoted CD8+ T cell infiltration into the tumor and systemic dendritic cell maturation. Particularly, HANPs bearing the highest aspect ratio exhibited the strongest immunomodulatory and anti-tumor function. This study suggested the potential of HANPs to be a safe and effective drug-free nanomaterial to control the TIM for OS therapy. STATEMENT OF SIGNIFICANCE: Emerging studies demonstrated that hydroxyapatite nanoparticles (HANPs) inhibited tumor cell proliferation and tumor growth. However, the underlying anti-tumor mechanism still remains unclear, and the capacity of HANPs without any other additive to regulate tumor immune microenvironment (TIM) was scarcely reported before. Herein, we demonstrated that HANPs, in an aspect ratio-dependent manner, showed the potential to delay the growth of osteosarcoma (OS) and to regulate TIM by promoting the invasion of CD8+ T cells and F4/80+ macrophages, and inducing immunogenic cell death (ICD) in tumors. This work revealed the new molecular mechanism for HANPs against OS, and suggested HANPs might be a novel ICD inducer for OS treatment.
