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基于人源 3D 表皮模型的金纳米颗粒的表皮渗透及其作用机制。

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

机构信息

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , Beijing 100085, China.

College of Resources and Environment, University of Chinese Academy of Sciences , Beijing 100049, China.

出版信息

ACS Appl Mater Interfaces. 2017 Dec 13;9(49):42577-42588. doi: 10.1021/acsami.7b13700. Epub 2017 Nov 29.

DOI:10.1021/acsami.7b13700
PMID:29148696
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.

摘要

纳米材料被广泛应用于各个领域,研究其穿过皮肤的迁移行为有助于了解相应的暴露风险。为了揭示纳米颗粒表面功能化如何影响皮肤渗透,本研究采用人重建 3D 表皮模型,研究了三种具有不同表面电荷的金纳米颗粒(GNPs),即十六烷基三甲基溴化铵(CTAB)包覆的 GNPs(CTAB@GNP)、聚乙烯吡咯烷酮(PVP)包覆的 GNPs(PVP@GNP)和柠檬酸(Citrate)包覆的 GNPs(Citrate@GNP)。Au 在表皮模型不同层中的分布测量表明,所有三种 GNPs 都可以穿透表皮,其中带正电荷的 CTAB@GNP 具有最高的皮肤渗透效率。介质蛋白的向上渗透证实了 GNP 处理引起的皮肤渗透的发生,并且 GNP 暴露导致角质层中的脂质网络发生改变。与 Citrate@GNP 和 PVP@GNP 相比,CTAB@GNP 显著破坏了角质形成细胞的紧密连接,导致纳米颗粒的细胞旁渗透。细胞质中存在金表明,通过内吞作用和外排作用的跨细胞途径是测试的 GNPs 穿过表皮的主要渗透行为。通过 3D 表皮模型研究 GNP 渗透过程,一方面为评估纳米颗粒穿过皮肤的迁移过程提供了一种有前途的方法,另一方面为具有不同表面电荷的 GNPs 不同渗透行为提供了机制解释。本研究结果将有助于纳米技术的改进和纳米安全性评估。

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