Hypothesis: Gold nanoparticles (GNP) are considered an ideal model to help understanding the nano-skin interface. The surface functionality of gold nanorods (GNR) is expected to influence the uptake of nanoparticles into specific targets of skin such as hair follicles or dermis. Hence, it should be possible to modify the surface chemistry of GNP to achieve more targeted and safe skin therapy. Experiments: GNR functionalized with various surface ligands (neutral, anionic, cationic, and hydrophobic) were evaluated for their accumulation into hair follicles of human skin sheets using ex-vivo setup. The extent of GNR accumulation into hair follicles and other skin compartments was quantified by inductively coupled plasma-optical emission spectroscopy (ICP-OES), and their spatial distribution through skin layers was investigated by laser ablation-inductively coupled plasma-mass spectroscopy (LA-ICP-MS). Results: The lipophilic properties of sebum-rich hair follicles enhanced the accumulation of hydrophobic polystyrene (PS)-GNR into hair follicles (similar to 13% of the total applied dose), while neutral polyethylene glycol (PEG)-GNR were distributed into all skin compartments, especially the dermis (similar to 11.5% of the total applied dose), which exhibits hydrophilic characteristics. Charged GNR showed a negligible percentage of penetration into any of the skin compartments. GNR could be a promising approach for targeted skin disease treatment and transdermal administration of drugs and therapy. (C) 2017 Elsevier Inc. All rights reserved.