Preferential Accumulation of Phospholipid-PEG and Cholesterol-PEG Decorated Gold Nanorods into Human Skin Layers and Their Photothermal-Based Antibacterial Activity
Authors: Rania Hamed
Jamila Isabilla Ali
Amal G Al-Bakri
Enam A Khalil
Nouf N Mahmoud
Ala A Alhusban
Journal: Scientific Reports (2019)
Discipline: Multidisciplinary
Keywords: gold nanorods; polyethylene glycol-thiol; skin penetration; excised human skin layers; colloidal stability
Affiliations: Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, 11733, Jordan. ., Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, 11733, Jordan., Department of Pharmaceutics & Pharmaceutical Technology, School of Pharmacy, The University of Jordan, Amman, 11942, Jordan.

Abstract:  Herein, a library of gold nanorods (GNR) decorated with polyethylene glycol-thiol (PEG-SH) containing different functionalities were synthesized and characterized by optical absorption spectroscopy, zeta potential, dynamic light scattering (DLS), transmission electron microscope (TEM) and proton nuclear magnetic resonance (1H-NMR). The colloidal stability of GNR when exposed to skin, and their preferential accumulation into excised human skin layers were investigated. Confocal laser scanning microscopy, transmission electron microscope (TEM) and inductively coupled plasma-optical emission spectroscopy (ICP-OES) were utilized to track the penetration of GNR into different skin layers. The results demonstrated that cholesterol-PEG coated GNR were preferentially loaded up in the upper layers of skin (stratum corneum), while phospholipid-PEG coated counterparts were drastically deposited in skin dermis. Neutral methoxy-PEG-coated GNR were distributed in both SC and dermis skin layers, while charged GNR (anionic-carboxylic acid-PEG-GNR and cationic-amine-PEG-GNR) revealed a minimal accumulation into skin. DSPE-PEG-GNR and Chol-PEG-GNR demonstrated antibacterial activities against Staphylococcus aureus (S aureus) at MIC values of 0.011 nM and 0.75 nM, respectively. Photothermal treatment for S. aureus at sub-MIC concentrations resulted in a significant bactericidal effect when using Chol-PEG-GNR but not DSPE-PEG-GNR. Gold-based nanoscale systems have great value as a promising platform for skin diseases therapy. 

Retracted: No

PubPeer comments:
 There are a couple of things that lead me to believe that the two spectra in 4(c) are not the same sample: **(1) ** The peak at ~570 nm associated with non-rodlike impurities seems to disappear after after 24 h. ![file] **(2)** The NIR peak has broadened, yet the absorbance at 400 nm is the same (implying that the conc. of Au is the same). I would expect the relative height of the NIR peak to decrease relative to 400 nm (since the spectrum is normalised, this should have manifested as an increase in the absorbance at 400 nm). The point about relative heights of peaks not being consistent with what I would expect is also true for 4(a), (b) and (f). 4(e) shows very little broadening, but a substantial increase in the absorbance at 400 nm, which also strikes me as inconsistent with what would be expected. , 
 #1 Thank you for your comment. The gold nanorods were exposed to excised human skin, and all the samples demonstrated good colloidal stability upon contact with skin without any significant aggregation. The relative height of the NIR peak did not decrease or decreased slightly relative to 500 nm in all the samples except sample 4e, and the slight broadening or shifting of the longitudinal peaks is most likely due to the change in refractive index of the surrounding media as the particles were in direct contact with human skin. Consequently, we could not predict changes in abs at 500 nm in all cases (the peaks at 500 nm in 4b and 4c were increased slightly). The spectra in Fig 4c are for the same sample which contains trace of impurities (irregular or non-rods particles); since the nanoparticles were exposed to human skin, the interaction of these impurities with skin elements (possible adsorption onto the skin surface or even absorption) could not be excluded. Similar behaviour is also observed in 4b, and observed in our current study of GNR with rat skin. For sample 4e, the nanoparticles were dispersed in toluene, and upon skin exposure, the NIR height was decreased greatly relative to 500 nm; although it showed a slight shift in NIR peak, similar behaviour was observed for BSA-GNR when exposed to cell culture media, and for GNR dispersed in DCM and exposed to skin. ,