TY - JOUR
T1 - The role of NLRP3 inflammasome activation in proinflammatory and cytotoxic effects of metal nanoparticles
AU - Aschner, Michael
AU - Skalny, Anatoly V.
AU - Martins, Airton C.
AU - Tizabi, Yousef
AU - Zaitseva, Irina P.
AU - Santamaria, Abel
AU - Lu, Rongzhu
AU - Gluhcheva, Yordanka Y.
AU - Tinkov, Alexey A.
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.
PY - 2025/4
Y1 - 2025/4
N2 - Exposure to metal nanoparticles (NPs) is known to induce inflammatory responses in various tissues, thus limiting their therapeutic potential. NOD-like receptor protein 3 (NLRP3) inflammasome activation is an essential component of innate immunity playing a significant role in inflammation and development of inflammatory diseases. Therefore, the objective of the present review was to summarize data on the role of NLRP3 inflammasome in proinflammatory effects induced by metal NPs, and to discuss the underlying molecular mechanisms, including its dependence on the physical and chemical properties of metal NPs. Titanium, zinc, silver, aluminum, iron, cobalt, nickel, vanadium, and tungsten nanoparticles, as well as metal-based quantum dots have all been shown to induce NLRP3 inflammasome activation in vitro in macrophages and monocytes, dendritic cells, keratinocytes, hepatocytes, enterocytes, microglia, astrocytes, lung epithelial cells, endotheliocytes, as well as certain types of cancer cells. In vivo studies confirmed the role of NLRP3 pathway activation in development of colitis, pulmonary inflammation, liver damage, osteolysis, and neuroinflammation induced by various metal nanoparticles. Briefly, particle endocytosis with subsequent lysosomal damage, induction of ROS formation, K+ efflux, increased intracellular Ca2+ levels, and NF-κB pathway activation results in NLRP3 inflammasome complex assembly, caspase-1 activation, and cleavage of pro-IL-1β and pro-IL-18 to mature proinflammatory cytokines, while gasdermin D cleavage induces pyroptotic cell death. Moreover, small-sized and rod-shaped metal NPs exert a more profound stimulatory effect on NLRP3 inflammasome activation, but contrary findings have also been reported. Taken together, it is concluded that NLRP3 inflammasome may mediate both adverse proinflammatory effects of metal nanoparticles, as well as their beneficial effect when used as antitumor agents.
AB - Exposure to metal nanoparticles (NPs) is known to induce inflammatory responses in various tissues, thus limiting their therapeutic potential. NOD-like receptor protein 3 (NLRP3) inflammasome activation is an essential component of innate immunity playing a significant role in inflammation and development of inflammatory diseases. Therefore, the objective of the present review was to summarize data on the role of NLRP3 inflammasome in proinflammatory effects induced by metal NPs, and to discuss the underlying molecular mechanisms, including its dependence on the physical and chemical properties of metal NPs. Titanium, zinc, silver, aluminum, iron, cobalt, nickel, vanadium, and tungsten nanoparticles, as well as metal-based quantum dots have all been shown to induce NLRP3 inflammasome activation in vitro in macrophages and monocytes, dendritic cells, keratinocytes, hepatocytes, enterocytes, microglia, astrocytes, lung epithelial cells, endotheliocytes, as well as certain types of cancer cells. In vivo studies confirmed the role of NLRP3 pathway activation in development of colitis, pulmonary inflammation, liver damage, osteolysis, and neuroinflammation induced by various metal nanoparticles. Briefly, particle endocytosis with subsequent lysosomal damage, induction of ROS formation, K+ efflux, increased intracellular Ca2+ levels, and NF-κB pathway activation results in NLRP3 inflammasome complex assembly, caspase-1 activation, and cleavage of pro-IL-1β and pro-IL-18 to mature proinflammatory cytokines, while gasdermin D cleavage induces pyroptotic cell death. Moreover, small-sized and rod-shaped metal NPs exert a more profound stimulatory effect on NLRP3 inflammasome activation, but contrary findings have also been reported. Taken together, it is concluded that NLRP3 inflammasome may mediate both adverse proinflammatory effects of metal nanoparticles, as well as their beneficial effect when used as antitumor agents.
KW - Inflammation
KW - Metal nanoparticles
KW - Pyroptosis
KW - Quantum dots
KW - Toxicity
UR - https://www.scopus.com/pages/publications/85218215373
UR - https://www.scopus.com/pages/publications/85218215373#tab=citedBy
U2 - 10.1007/s00204-025-03972-x
DO - 10.1007/s00204-025-03972-x
M3 - Review article
C2 - 39960653
AN - SCOPUS:85218215373
SN - 0340-5761
VL - 99
SP - 1287
EP - 1314
JO - Archives of Toxicology
JF - Archives of Toxicology
IS - 4
M1 - 153869
ER -
