Epidermal Penetration of Gold Nanoparticles and Its Underlying Mechanism Based on Human Reconstructed 3D Episkin Model

Abstract

Nanomaterials are widely used in diverse aspects, and their translocation behavior through the skin would be helpful in understanding the corresponding exposure risks. To reveal how surface functionalization of nanoparticles influences the skin penetration, three kinds of gold nanoparticles (GNPs) with negatively, neutrally, and positively charged surfaces, that is, cetyltrimethylammonium bromide-coated GNPs (CTAB@GNP), polyvinylpyrrolidone-coated GNPs (PVP@GNP), and citrate-coated GNPs (Citrate@GNP), were studied using human reconstructed 3D Episkin model. The measurement of Au distribution in diverse layers of the Episkin model indicated that all three GNPs could penetrate through the epidermis, wherein CTAB@GNP with positive surface charges exhibited the highest efficiency in skin penetration. The upward osmosis of the medium proteins confirmed the occurrence of skin permeation induced by GNP treatment, and the lipid network in the stratum corneum was also altered as the consequence of GNP exposure. When compared to Citrate@GNP and PVP@GNP, CTAB@GNP significantly compromised the tight junction of keratinocytes, causing paracellular penetration of nanoparticles. The existence of cytoplasmic gold showed the transcytosis pathway through endocytosis and exocytosis processes was the main epidermic penetration behavior of the tested GNPs. The study on GNP penetration process through the 3D Episkin model has, on one hand, offered a promising approach to evaluate the translocation process of nanoparticles across the skin, and, on the other hand, provided mechanism explanation for diverse penetration behaviors of GNPs with different surface charges. The findings herein would be of great help in nanotechnology improvement and nanosafety evaluation.

Keywords: 3D Episkin model; epidermal penetration; gold nanoparticles; lipid network; paracellular and transcellular transport.