Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
Proc Natl Acad Sci U S A. 2021 Nov 2;118(44). doi: 10.1073/pnas.2108131118.
The rapid development of nanotechnology has greatly benefited modern science and engineering and also led to an increased environmental exposure to nanoparticles (NPs). While recent research has established a correlation between the exposure of NPs and cardiovascular diseases, the intrinsic mechanisms of such a connection remain unclear. Inhaled NPs can penetrate the air-blood barrier from the lung to systemic circulation, thereby intruding the cardiovascular system and generating cardiotoxic effects. In this study, on-site cardiovascular damage was observed in mice upon respiratory exposure of silica nanoparticles (SiNPs), and the corresponding mechanism was investigated by focusing on the interaction of SiNPs and their encountered biomacromolecules en route. SiNPs were found to collect a significant amount of apolipoprotein A-I (Apo A-I) from the blood, in particular when the SiNPs were preadsorbed with pulmonary surfactants. While the adsorbed Apo A-I ameliorated the cytotoxic and proinflammatory effects of SiNPs, the protein was eliminated from the blood upon clearance of the NPs. However, supplementation of Apo A-I mimic peptide mitigated the atherosclerotic lesion induced by SiNPs. In addition, we found a further declined plasma Apo A-I level in clinical silicosis patients than coronary heart disease patients, suggesting clearance of SiNPs sequestered Apo A-I to compromise the coronal protein's regular biological functions. Together, this study has provided evidence that the protein corona of SiNPs acquired in the blood depletes Apo A-I, a biomarker for prediction of cardiovascular diseases, which gives rise to unexpected toxic effects of the nanoparticles.
纳米技术的快速发展极大地促进了现代科学和工程的发展，也导致了人们接触纳米颗粒（NPs）的机会增加。虽然最近的研究已经确定了 NPs 暴露与心血管疾病之间的相关性，但这种关联的内在机制尚不清楚。吸入的 NPs 可以从肺部穿透空气-血液屏障进入全身循环，从而侵入心血管系统并产生心脏毒性作用。在这项研究中，我们观察到小鼠在呼吸暴露于硅纳米颗粒（SiNPs）后出现了即时的心血管损伤，并通过聚焦 SiNPs 与它们在途中遇到的生物大分子的相互作用来研究相应的机制。研究发现，SiNPs 从血液中大量收集载脂蛋白 A-I（Apo A-I），特别是当 SiNPs 预先被肺表面活性剂吸附时。虽然吸附的 Apo A-I 减轻了 SiNPs 的细胞毒性和促炎作用，但当 NPs 被清除时，该蛋白从血液中被清除。然而，Apo A-I 模拟肽的补充减轻了 SiNPs 诱导的动脉粥样硬化病变。此外，我们发现临床矽肺患者的血浆 Apo A-I 水平进一步下降，低于冠心病患者，这表明 SiNPs 隔离的 Apo A-I 被清除，从而损害了该冠状蛋白的正常生物学功能。总之，这项研究提供了证据表明，血液中获得的 SiNPs 蛋白冠会耗尽 Apo A-I，这是预测心血管疾病的生物标志物，从而导致纳米颗粒产生意想不到的毒性作用。
