Amorphous silica nanoparticles size-dependently aggravate atopic dermatitis-like skin lesions following an intradermal injection

Abstract

BackgroundDue to the rising use of nanomaterials (NMs), there is concern that NMs induce undesirable biological effects because of their unique physicochemical properties. Recently, we reported that amorphous silica nanoparticles (nSPs), which are one of the most widely used NMs, can penetrate the skin barrier and induce various biological effects, including an immune-modulating effect. Thus, it should be clarified whether nSPs can be a risk factor for the aggravation of skin immune diseases. Thus, in this study, we investigated the relationship between the size of SPs and adjuvant activity using a model for atopic dermatitis.ResultsWe investigated the effects of nSPs on the AD induced by intradermaly injected-mite antigen Dermatophagoides pteronyssinus (Dp) in NC/Nga mice. Ear thickness measurements and histopathological analysis revealed that a combined injection of amorphous silica particles (SPs) and Dp induced aggravation of AD in an SP size-dependent manner compared to that of Dp alone. In particular, aggravation was observed remarkably in nSP-injected groups. Furthermore, these effects were correlated with the excessive induction of total IgE and a stronger systemic Th2 response. We demonstrated that these results are associated with the induction of IL-18 and thymic stromal lymphopoietin (TSLP) in the skin lesions.ConclusionsA particle size reduction in silica particles enhanced IL-18 and TSLP production, which leads to systemic Th2 response and aggravation of AD-like skin lesions as induced by Dp antigen treatment. We believe that appropriate regulation of nanoparticle physicochemical properties, including sizes, is a critical determinant for the design of safer forms of NMs.

Perturbation of physiological systems by nanoparticles

“…351 Although nanoparticle-induced atopic dermatitis has not been reported, some nanoparticles, including TiO 2 , polystyrene, and amorphous SiO 2 nanoparticles, exacerbate atopic dermatitis by acting as allergens after intradermal injection. [352][353][354] This activity may further enhance the excessive induction of total IgE and cause a stronger systemic Th2 response. 354 Phototoxicity describes an inflammatory skin reaction that results from the topical application of chemical substances and subsequent exposure to light, particularly ultraviolet A radiation (320-400 nm).…”

“…[352][353][354] This activity may further enhance the excessive induction of total IgE and cause a stronger systemic Th2 response. 354 Phototoxicity describes an inflammatory skin reaction that results from the topical application of chemical substances and subsequent exposure to light, particularly ultraviolet A radiation (320-400 nm). 355 Because some nanoparticles are used in cosmetics, their potential phototoxicity is a matter of concern.…”

Nano-safety Research: Examining the Associations among the Biological Effects of Nanoparticles and Their Physicochemical Properties and Kinetics

“…For example, we have reported that amorphous silica nanoparticles (diameter less than 100 nm), unlike the bulk material, can enter the sys-temic circulation through the skin and nasal or oral mucosa and be distributed to several tissues such as liver or brain. [11][12][13] We have also reported that in mice silica nanoparticles with diameter of 70 nm can cross the placental barrier and migrate to the fetal brain and liver, 14) and that systemic administration of the silica nanoparticles impairs blood clotting, induces disseminated intravascular coagulation syndrome, and injures the placenta resulting in intrauterine growth restriction and developmental neurotoxicity in the fetus. 14,15) 2.1.…”

Toxicity of thiolated silica nanoparticles modified with sulfobetaine methacrylate for potential use in chemotherapy drug conjugation

“…Almost all NPs that are administrated systematically are coated with electrically neutral hydrophobic surface layers called a "stealth coating" which extends the half-life of NPs to >40 h (Moghimi et al, 2001). Administration of NPs via intradermal or subcutaneous injection showed a different distribution depending on the absence or presence of coatings (Hirai et al, 2012;Liu et al, 2014). The degree of NPs coating plays an important factor in reaching targeted tissues (Liu et al, 2014).…”

“…However, antiangiogenic factors can cause incompatible expansion and defects in the architecture of tumour vasculature (Fukumura and Jain, 2007;Hanahan and Folkman, 1996). Studies using transplanted rodent tumours revealed that the pore size of tumours microvessels range between 100 nm to 780 nm in diameter, therefore; this is an important feature in the extravasation of NPs (Hobbs et al, 1998;Li and Huang, 2010). Additionally, tumours commonly have poor lymphatic drainage, which can reduce the removal of NPs (Maeda et al, 2000).…”