Key Laboratory of Environment Remediation and Ecological Health, Ministry of Education, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
Department of Environmental Sciences, University of Houston-Clear Lake, 2700 Bay Area Blvd., Houston, Texas 77058, USA.
Nanoscale. 2021 May 20;13(19):9018-9030. doi: 10.1039/d1nr01965a.
Black phosphorus (BP) nanomaterials have shown great potential in versatile applications including biomedicine and potentially interact with vessel walls following intravenous injection in biomedical usage or environmental exposure. However, it remains unknown whether the exposure to BP nanomaterials induces alterations of the endothelium and further vascular injury. Herein, the endothelial function of human umbilical vein endothelial cells (HUVECs) and the structure and transcriptome of C57BL/6 mouse aortas are evaluated after the exposure to BP quantum dots (BPQDs) and nanosheets (BPNSs). BPNSs with irregular shapes and larger lateral size are more prone to inhibit in vitro angiogenesis at non-cytotoxic concentrations and markedly trigger platelet adhesion to HUVECs compared to BPQDs. Decreased nitric oxide (NO) production resulting from endothelial NO synthase (eNOS) dysregulation is involved in the BP-induced endothelial dysfunction. Both BPQDs and BPNSs at 0.8 and 6.4 μg mL-1 inhibit eNOS enzymatic activity through dephosphorylation of eNOS-Ser1177 and phosphorylation of eNOS-Thr495, but unlike BPQDs, BPNSs also downregulate eNOS expression. Despite no pathological damage in the structure of mouse aortas, BPQDs and BPNSs trigger aberration of aortic transcriptome involved in vasoconstriction abnormality, metabolic disturbance, and immune perturbation. This study demonstrates the adverse effect of BP nanomaterials on vasculature, and suggests that the morphological attribute of BP plays a crucial role in the vascular risks.
黑磷（BP）纳米材料在包括生物医药在内的多个领域具有广泛的应用前景，并且在生物医药应用或环境暴露中静脉注射后可能与血管壁相互作用。然而，目前尚不清楚暴露于 BP 纳米材料是否会引起内皮细胞的改变和进一步的血管损伤。在此，我们评估了人类脐静脉内皮细胞（HUVEC）的内皮功能以及 C57BL/6 小鼠主动脉的结构和转录组，这些细胞和组织在暴露于 BP 量子点（BPQDs）和纳米片（BPNSs）后会发生变化。与 BPQDs 相比，具有不规则形状和更大侧向尺寸的 BPNSs 在非细胞毒性浓度下更倾向于抑制体外血管生成，并显著引发血小板黏附到 HUVECs。内皮型一氧化氮合酶（eNOS）失调导致的一氧化氮（NO）产生减少参与了 BP 引起的内皮功能障碍。在 0.8 和 6.4μg·mL-1 浓度下，BPQDs 和 BPNSs 均通过使 eNOS-Ser1177 去磷酸化和 eNOS-Thr495 磷酸化来抑制 eNOS 酶活性，但与 BPQDs 不同的是，BPNSs 还下调了 eNOS 表达。尽管小鼠主动脉的结构没有出现病理损伤，但 BPQDs 和 BPNSs 引发了与血管收缩异常、代谢紊乱和免疫失调相关的主动脉转录组异常。本研究表明 BP 纳米材料对血管系统具有不良影响，并提示 BP 的形态属性在血管风险中起着关键作用。
