Nanomedicine Lab, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, U.K.
National Graphene Institute, The University of Manchester, Manchester, M13 9PL, U.K.
ACS Nano. 2023 Dec 26;17(24):24919-24935. doi: 10.1021/acsnano.3c06599. Epub 2023 Dec 5.
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 (-BN) nanosheets and boron nitride nanotubes (BNNTs) in mice. Animals were exposed by single oropharyngeal aspiration to -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 (., immune response, histopathology, tissue remodeling, and genotoxicity). On the other hand, material deposition and clearance from the lungs were assessed. Two-dimensional -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 -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.
氮化硼（BN）纳米材料在材料科学界引起了广泛关注。然而，仍需要广泛的研究来彻底分析它们的安全概况。在这里，我们研究了二维六方氮化硼（-BN）纳米片和氮化硼纳米管（BNNTs）在小鼠中的肺部影响和清除。动物通过单次经口吸入暴露于 -BN 或 BNNTs。在第 1、7 和 28 天收集支气管肺泡灌洗液（BAL）和肺。一方面，通过各种方法评估对肺部的不利影响（例如免疫反应、组织病理学、组织重塑和遗传毒性）。另一方面，评估材料在肺部的沉积和清除。二维 -BN 没有引起任何明显的免疫反应或肺部损伤，尽管拉曼光谱证实了材料的存在。此外，低纵横比的 -BN 纳米片被肺泡中存在的吞噬细胞迅速内化，从而从肺部有效清除。相比之下，高纵横比的 BNNTs 引起强烈且持久的炎症反应，特征是暴露后 28 天内持续炎症和固有免疫和适应性免疫的激活。此外，在这些材料中还证明了肺部实质中存在肉芽肿结构和正在进行的纤维化以及 DNA 损伤。同时，BNNTs 在肺切片中被识别长达 28 天，表明具有较长的生物持久性，正如以前对其他具有较差肺部清除率的高纵横比纳米材料（如多壁碳纳米管（MWCNTs））所证明的那样。总体而言，与它们的纳米管对应物相比，我们揭示了 BN 基二维纳米片更安全的毒理学特征。我们还报告了 BNNTs 和 MWCNTs 在肺部反应方面的强相似性，强调了它们的高纵横比作为其毒性的主要驱动因素。
