Abstract

Over the past decade, a vast array of nanomaterials has been created through the development of nanotechnology. With the increasing application of these nanomaterials in various fields, such as foods, cosmetics, and medicines, there has been concern about their safety, that is, nanotoxicity. Therefore, there is an urgent need to collect information about the biological effects of nanomaterials so that we can exploit their potential benefits and design safer nanomaterials, while avoiding nanotoxicity as a result of inhalation or skin exposure. In particular, the immunomodulating effect of nanomaterials is one of most interesting aspects of nanotoxicity. However, the immunomodulating effects of nanomaterials through skin exposure have not been adequately discussed compared with the effects of inhalation exposure, because skin penetration by nanomaterials is thought to be extremely low under normal conditions. On the other hand, the immunomodulatory effects of nanomaterials via skin may cause severe problems for people with impaired skin barrier function, because some nanomaterials could penetrate the deep layers of their allergic or damaged skin. In addition, some studies, including ours, have shown that nanomaterials could exhibit significant immunomodulating effects even if they do not penetrate the skin. In this review, we summarize our current knowledge of the allergic responses induced by nanomaterials upon skin exposure. First, we discuss nanomaterial penetration of the intact or impaired skin barrier. Next, we describe the immunomodulating effects of nanomaterials, focusing on the sensitization potential of nanomaterials and the effects of co-exposure of nanomaterials with substances such as chemical sensitizers or allergens, on the onset of allergy, following skin exposure. Finally, we discuss the potential mechanisms underlying the immunomodulating effects of nanomaterials by describing the involvement of the protein corona in the interaction of nanomaterials with biological components and by presenting recent data about the adjuvant effects of well-characterized particle adjuvant, aluminum salt, as an example of immunomodulatory particulate.

Highlights

  • Advances in nanotechnology have made possible the design and production of many engineered nanomaterials— nanoparticles, nanofibers, and nanosheets—which are defined as materials with structures having at least one dimension less than 100 nm [1, 2]

  • These products have become indispensable in various fields, such as electronics, foods, cosmetics, and medicines, because nanomaterials have unique physicochemical properties and exert innovative functions compared with conventional larger particles; these properties and functions include enhanced electrical conductivity, tensile strength, and chemical reactivity, and stem from an increase in the surface area per unit weight compared with a larger amount (>100 nm) of the same material [3, 4]

  • There is an urgent need to understand the immunomodulatory effects of nanomaterials upon skin exposure, effects that may lead to the onset or aggravation of allergy

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Summary

INTRODUCTION

Advances in nanotechnology have made possible the design and production of many engineered nanomaterials— nanoparticles, nanofibers, and nanosheets—which are defined as materials with structures having at least one dimension less than 100 nm [1, 2] These products have become indispensable in various fields, such as electronics, foods, cosmetics, and medicines, because nanomaterials have unique physicochemical properties and exert innovative functions compared with conventional larger particles; these properties and functions include enhanced electrical conductivity, tensile strength, and chemical reactivity, and stem from an increase in the surface area per unit weight compared with a larger amount (>100 nm) of the same material [3, 4]. Individuals who used a facial soap containing hydrolyzed wheat protein were presumed to be sensitized to this protein [23, 24] Given these findings, there is an urgent need to understand the immunomodulatory effects of nanomaterials upon skin exposure, effects that may lead to the onset or aggravation of allergy. We discuss potential mechanisms underlying the immunomodulating effects of nanomaterials by describing the involvement of the protein corona in the interaction of nanomaterials with complement proteins and by presenting recent study about the adjuvant effects of aluminum salts, which are well characterized in basic immunology

SKIN STRUCTURE AND PENETRATION OF SKIN BY NANOMATERIALS
SENSITIZATION POTENTIAL OF NANOMATERIALS ON SKIN
COMBINED EXPOSURE TO NANOMATERIALS AND OTHER SUBSTANCES
IMMUNOMODULATING MECHANISMS OF THE ADJUVANT EFFECTS OF PARTICLES
Findings
FUTURE PROSPECTS AND CONCLUSION
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