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Aspect ratio-dependent dual-regulation of the tumor immune microenvironment against osteosarcoma by hydroxyapatite nanoparticles

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机构： [1]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China, 610064 [2]NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterials & Institute of Regulatory Science for Medical Devices & NMPA Research Base of Regulatory Science for Medical Devices, Sichuan University, Chengdu, China, 610064 [3]Provincial Engineering Research Center for Biomaterials Genome of Sichuan & Research Center for Materials Genome Engineering, Sichuan University, Chengdu, China, 610064 [4]Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China, 610041 [5]College of Biomedical Engineering, Sichuan University, Chengdu, China, 610064 [6]Medical School, Kunming University of Science and Technology, Kunming, China, 650500 [7]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan University, Chengdu, China, 610041

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关键词： hydroxyapatite nanoparticles aspect ratio immunogenic cell death macrophage polarization tumor immune microenvironment

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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.Copyright © 2023. Published by Elsevier Ltd.

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出版当年[2023]版：

大类 | 1 区

医学

小类 | 1 区工程：生物医学 1 区材料科学：生物材料

最新[2023]版：

大类 | 1 区

医学

小类 | 1 区工程：生物医学 1 区材料科学：生物材料

第一作者：

第一作者机构： [1]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China, 610064 [5]College of Biomedical Engineering, Sichuan University, Chengdu, China, 610064 [6]Medical School, Kunming University of Science and Technology, Kunming, China, 650500

通讯作者：

通讯机构： [1]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China, 610064 [2]NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterials & Institute of Regulatory Science for Medical Devices & NMPA Research Base of Regulatory Science for Medical Devices, Sichuan University, Chengdu, China, 610064 [3]Provincial Engineering Research Center for Biomaterials Genome of Sichuan & Research Center for Materials Genome Engineering, Sichuan University, Chengdu, China, 610064 [5]College of Biomedical Engineering, Sichuan University, Chengdu, China, 610064

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Aspect ratio-dependent dual-regulation of the tumor immune microenvironment against osteosarcoma by hydroxyapatite nanoparticles

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