Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan.
Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien, Taiwan.
Front Immunol. 2022 Apr 4;13:806686. doi: 10.3389/fimmu.2022.806686. eCollection 2022.
Nanodiamond (ND) has been developed as a carrier to conduct various diagnostic and therapeutic uses. Safety is one of the major considerations, while the hemocompatibility of ND is not clearly addressed. Here we found that, compared to the other sizes of ND with relatively inert properties, treatments of 50 nm ND induced stronger platelet aggregation, platelet pyroptosis, apoptosis and thrombocytopenia in mice. Blockage treatments of soluble P-selectin, reactive oxygen species (ROS), and Nlrp3 inflammasome inhibitors markedly suppressed such adverse effects, suggesting ND-induced platelet activation and pyroptosis involves surface P-selectin-mediated enhancement of mitochondrial superoxide levels and Nlrp3 inflammasome activation. In addition, challenges of NDs induced less platelet pyroptosis and displayed less thrombocytopenia in P-selectin ( ), Nlrp3 ( ) and caspase-1 ( ) mutants, as compared to the wild type mice. Blockers of P-selectin, ROS, and Nlrp3 inflammasome pathways could be considered as antidotes for ND induced platelet activation and thrombocytopenia.
纳米金刚石（ND）已被开发为载体，用于进行各种诊断和治疗用途。安全性是主要考虑因素之一，而 ND 的血液相容性尚未得到明确解决。在这里，我们发现与具有相对惰性性质的其他尺寸 ND 相比，50nmND 的处理在小鼠中引起更强的血小板聚集、血小板细胞焦亡、细胞凋亡和血小板减少症。可溶性 P 选择素、活性氧（ROS）和 Nlrp3 炎性小体抑制剂的阻断处理显着抑制了这种不良反应，表明 ND 诱导的血小板活化和细胞焦亡涉及表面 P 选择素介导的线粒体超氧水平增强和 Nlrp3 炎性小体激活。此外，与野生型小鼠相比，P-选择素（ ）、Nlrp3（ ）和半胱天冬酶-1（ ）突变体的 ND 挑战引起的血小板细胞焦亡较少，血小板减少症也较少。P 选择素、ROS 和 Nlrp3 炎性小体途径的抑制剂可被视为治疗 ND 诱导的血小板活化和血小板减少症的解毒剂。
