Suppression of nanosilica particle-induced inflammation by surface modification of the particles

Abstract

It has gradually become evident that nanomaterials, which are widely used in cosmetics, foods, and medicinal products, could induce substantial inflammation. However, the roles played by the physical characteristics of nanomaterials in inflammatory responses have not been elucidated. Here, we examined how particle size and surface modification influenced the inflammatory effects of nanosilica particles, and we investigated the mechanisms by which the particles induced inflammation. We compared the inflammatory effects of silica particles with diameters of 30-1,000 nm in vitro and in vivo. In macrophages in vitro, 30- and 70-nm nanosilica particles (nSP30 and nSP70) induced higher production of tumor necrosis factor-α (TNFα) than did larger particles. In addition, intraperitoneal injection of nSP30 and nSP70 induced stronger inflammatory responses involving cytokine production than did larger particles in mice. nSP70-induced TNFα production in macrophage depended on the production of reactive oxygen species and the activation of mitogen-activated protein kinases (MAPKs). Furthermore, nSP70-induced inflammatory responses were dramatically suppressed by surface modification of the particles with carboxyl groups in vitro and in vivo; the mechanism of the suppression involved reduction in MAPK activation. These results provide basic information that will be useful for the development of safe nanomaterials.

Analysis of Skin Permeability and Toxicological Properties of Amorphous Silica Particles

“…Several reports have demonstrated that the characteristics of NMs, such as surface properties and size, are important factors for the induction of pharmacologic or pharmacokinetic alterations and cellular responses. [12][13][14][15] Three types of nSP70 were used in this experiment: unmodified nSP70, carboxyl group-modified nSP70 (nSP70-C), and amino group-modified nSP70 (nSP-70-N).…”

“…[7][8][9][10][11] In addition, some reports suggest that the size and surface properties of NMs are important for inducing pharmacologic or pharmacokinetic alterations and cellular responses. [12][13][14][15] These suggest that NMs can cause unexpected adverse reactions when they invade the body. Therefore, basic information about the characteristics of NMs and their in vivo and in vitro application is essential for the development of safe NMs.…”

Genotoxic and Biological Evaluation of a Nano Silica Cross Linked Composite Specifically Used for Intra-Vas Device

“…Cytotoxicity profile of silica nanoparticles has received experimental support in different model cell lines, which was considered to be the result of size-/dose-dependent effect and oxidative stress provoked by these particles [13]. Whereas Morishige T. et al [14] did not observe cell death when treated with silica nanoparticles (30-, 50-, 70-nm). On the other hand, a recent study reported that amorphous silica nanoparticles elicited chromosomal aberrations and gene mutations [15].…”

Efecto inmunomodulador de nanopartículas usadas en nanomedicina

“…Otros estudios indican que las NP de sílice pueden favorecer respuestas inmunes alérgicas de tipo Th2 en ratones expuestos a OVA, induciendo mayores niveles de inmunoglobulinas IgE, IgG e IgG1 (47). Estas NP también inducen la producción de TNF-a dependiente de la producción de ROS y de la activación de las proteínas cinasas activadas por mitógenos (MAPK, por la sigla en inglés de mitogen-activated protein kinases) en macrófagos, activando una respuesta inflamatoria (48,49). Chen y colaboradores (50) mostraron que cé-lulas de Kupffer estimuladas con NP de sílice liberan grandes cantidades de ROS, TNF-a y óxido nítrico causando inflamación.…”

“…Passagne y colaboradores (54) encontraron que las NP de sílice inducen estrés oxidativo, dependiente del tiempo y de su tamaño. Igualmente, se ha demostrado que las NP de sílice no cristalina, de tamaño nano y submicrónico, pueden inducir una alta producción de IL-1β por mecanismos que implican la activación del inflamasoma NLRP3, en macrófagos murinos preactivados con LPS (55) y en macrófagos humanos (48,56,57). Por otro lado, Peeters y colaboradores (58) demostraron que las NP de sílice cristalina inducen la activación del inflamasoma NLRP3 en células humanas derivadas del epitelio bronquial.…”