Pulmonary Toxicity of Boron Nitride Nanomaterials Is Aspect Ratio Dependent.

Pulmonary Toxicity of Boron Nitride Nanomaterials Is Aspect Ratio Dependent.
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DOI:
10.1021/acsnano.3c06599
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发表时间:
2023-12-26
期刊:
影响因子:
17.1
通讯作者:
Bussy C
Bussy C
中科院分区:
材料科学1区
文献类型:
--
作者:
Visani de Luna LA;Loret T;He Y;Legnani M;Lin H;Galibert AM;Fordham A;Holme S;Del Rio Castillo AE;Bonaccorso F;Bianco A;Flahaut E;Kostarelos K;Bussy C

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氮化硼(BN)纳米材料在材料科学界引起了极大的兴趣。然而,仍需要广泛的研究来彻底分析它们的安全性。在这里,我们研究了二维六方氮化硼(h-BN)纳米片和氮化硼纳米管(BNNTs)对小鼠肺的撞击和清除。动物经口咽一次吸入h-BN或BNNTs。在第1、7和28天,收集支气管肺泡灌洗液(BAL)和肺组织。一方面,使用不同的方法(如免疫反应、组织病理学、组织重塑和遗传毒性)评估对肺的不良影响。另一方面,对肺部的物质沉积和清除进行了评估。二维h-BN没有引起任何明显的免疫反应或肺损伤,尽管拉曼光谱证实了材料的存在。此外,低长宽比的h-BN纳米片被肺泡中的吞噬细胞迅速内化,从而有效地从肺中清除。相比之下,高纵横比的BNNTs引起了强烈而持久的炎症反应,其特征是暴露后持续炎症长达28天,并激活了天然免疫和获得性免疫。此外,肉芽肿性结构的存在和持续纤维化的迹象以及肺实质中的DNA损伤都被这些材料所证实。同时,在肺切片中发现BNNTs长达28天,这表明BNNTs具有长期的生物持久性,就像以前对其他高纵横比但肺清晰度较差的纳米材料,如多壁碳纳米管(MWCNTs)所证明的那样。总体而言,我们揭示了与其对应的纳米管相比,基于BN的二维纳米片具有更安全的毒理学特征。我们还报道了BNNTs和MWCNTs在肺反应方面的强烈相似之处,强调它们的高纵横比是其毒性的主要驱动因素。
Boron nitride (BN) nanomaterials have drawn a lot of interest in the material science community. However, extensive research is still needed to thoroughly analyze their safety profiles. Herein, we investigated the pulmonary impact and clearance of two-dimensional hexagonal boron nitride (h-BN) nanosheets and boron nitride nanotubes (BNNTs) in mice. Animals were exposed by single oropharyngeal aspiration to h-BN or BNNTs. On days 1, 7, and 28, bronchoalveolar lavage (BAL) fluids and lungs were collected. On one hand, adverse effects on lungs were evaluated using various approaches (e.g., immune response, histopathology, tissue remodeling, and genotoxicity). On the other hand, material deposition and clearance from the lungs were assessed. Two-dimensional h-BN did not cause any significant immune response or lung damage, although the presence of materials was confirmed by Raman spectroscopy. In addition, the low aspect ratio h-BN nanosheets were internalized rapidly by phagocytic cells present in alveoli, resulting in efficient clearance from the lungs. In contrast, high aspect ratio BNNTs caused a strong and long-lasting inflammatory response, characterized by sustained inflammation up to 28 days after exposure and the activation of both innate and adaptive immunity. Moreover, the presence of granulomatous structures and an indication of ongoing fibrosis as well as DNA damage in the lung parenchyma were evidenced with these materials. Concurrently, BNNTs were identified in lung sections for up to 28 days, suggesting long-term biopersistence, as previously demonstrated for other high aspect ratio nanomaterials with poor lung clearance such as multiwalled carbon nanotubes (MWCNTs). Overall, we reveal the safer toxicological profile of BN-based two-dimensional nanosheets in comparison to their nanotube counterparts. We also report strong similarities between BNNTs and MWCNTs in lung response, emphasizing their high aspect ratio as a major driver of their toxicity.
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