Nano- and Microparticles and Their Role in Inflammation and Immune Response: Focus on Neutrophil Extracellular Traps

Nanodiamond-Induced Thrombocytopenia in Mice Involve P-Selectin-Dependent Nlrp3 Inflammasome-Mediated Platelet Aggregation, Pyroptosis and Apoptosis

“…Previous reports have indicated that nanomaterial-induced NETs are critical for the initiation of adverse effects in vivo ( 74 – 76 , 82 ). At the same time, platelets are involved in NET-related abnormal inflammation and coagulation ( 67 , 83 ).…”

“…Blockage of P-selectin and Nlrp3 inflammasome by treatments of rP-sel and Nlrp3 inflammasome inhibitors markedly suppressed the adverse effects. However, NDs were shown to trigger the formation of platelet aggregates and NETs; and NDs are not easy to be sequestered in vivo and excreted from the body, because of their non-biodegradable property ( 74 – 76 , 82 ). Consequently, despite of blockers of P-selectin and Nlrp3 inflammasome pathways displayed as antidotes of ND, these adverse effects prohibit the in vivo use of ND before the fundamental safety problems are solved.…”

Nanoparticles for stimulation of neutrophil extracellular trap‐mediated immunity

“…The particle size is a critical factor in this interaction; if the hydrophobic surface of the NP measures approximately 10-40 nm [25,28], it becomes covered by a lipid bilayer, causing membrane irregularities, leakage, and subsequent membrane recycling. This leads to membrane merging with lysosomes, causing secondary leakage in the formed secondary lysosome [12]. The leakage of cathepsins into the cytoplasm triggers mitochondrial damage [29], as exemplified in cases like oxalosis.…”

“…Smaller particles (<10 nm) are submerged in the lipid membrane bilayer, while larger particles (>50 nm) do not cause significant membrane curvature to induce leakage [12]. However, interactions of neutrophils with needle-like crystals, such as monosodium urate [30] and alum [18], suggest that the proposed size definition for activation holds true for any irregular or sharp part present in microcrystals.…”

“…When NETs are released in relatively small areas, macrophages can efficiently remove them, maintaining a precise balance between NET formation and silent clearance. Disruption of NET clearance, either due to overproduction or macrophage failure, results in a substantial accumulation of oxidized NET-derived ROS, leading to the generation of immunologically "new" epitopes [12]. Uncontrolled or excessive NET production can exacerbate inflammation, contribute to the spread of tumor metastases, cause thrombosis [12], and play a significant role in various lung pathologies such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, and COVID, as extensively discussed in [13], among other complications.…”