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Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

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Nội dung chi tiết: Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

DOI: 10.1002/ ((please add manuscript number))Article type: Full Paper.Interactions of Skin with Gold Nanoparticles of Different Surface Charge, Shape

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_finale and Functionality.Rate Fernandes, Neil R. Smyth, Otto L. Muskens, Simone Nitri, Amelie Heuer-Jungemann Michael R. Ardern-Jones, and Antonios G. Kana

ras*Ms. Rule Fernandes, Ms. Amelie Heuer-Jungemann, Prof. Otto L. Muskens, Dr. Antonios G.KanarasInstitute of Life Sciences, Physics and Astronomy, Fa Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

culty of Applied and Physical Sciences, University of Southampton, Southampton, S0171BJ, UKE-mail: a.kanaras@soton.ac.ukMr. Simone NittiIstituto Itali

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

ano di Technologia, Via Morego 30, 16163 Genova, ItalyDr. Neil R. Smyth, Faculty of Natural and Environmental Sciences, University of Southampton, so

DOI: 10.1002/ ((please add manuscript number))Article type: Full Paper.Interactions of Skin with Gold Nanoparticles of Different Surface Charge, Shape

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final: gold nanoparticles, peptides, functionality, skin penetrationAbstractWe investigate the interactions between skin and colloidal gold nanoparticles o

f different physicochemical characteristics. By systematically varying the charge, shape and functionality of gold nanoparticles, we assess the nanopa Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

rticle penetration through the different skin layers. The penetration is evaluated both qualitatively and quantitatively using a variety of complement

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

ary techniques. Inductively coupled plasma optical emission spectrometry (ICP-OES) is used to quantify the total number of particles penetrated into t

DOI: 10.1002/ ((please add manuscript number))Article type: Full Paper.Interactions of Skin with Gold Nanoparticles of Different Surface Charge, Shape

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_finalisualization of nanoparticle migration within the different skin substructures. Our studies reveal that gold nanoparticles functionalized with cell pe

netrating peptides (CPPs) TAT and R- are found in the skin in larger quantities than polyethylene glycol functionalized nanoparticles and are able to Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

enter deep1into the skin structure. The systematic studies presented in this work can be of strong interest for new developments in transdermal admini

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

stration of drugs and therapy.1. IntroductionThe utilization of nanoparticles in biomedicine holds potential for important developments in drug delive

DOI: 10.1002/ ((please add manuscript number))Article type: Full Paper.Interactions of Skin with Gold Nanoparticles of Different Surface Charge, Shape

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_finalzation which in many cases allow pre-designing the properties of the functional nanomaterial.15’121 Having available a rich library of nanomaterials,

one of the biggest challenges is to understand the nanoparticle behavior when introduced to biological structures.'13’141 Currently many studies focus Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

on how the morphology, charge and ligand capping of nanoparticles influence their cellular fate.'15-191 For example, in earlier work it was shown how

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

the physicochemical characteristics of gold nanoparticles impact on the number of particles taken up or exocytosed by endothelial cells.'20’ 211 It w

DOI: 10.1002/ ((please add manuscript number))Article type: Full Paper.Interactions of Skin with Gold Nanoparticles of Different Surface Charge, Shape

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_finalnderstanding the basic rules that govern nanoparticle-cell interactions at the subcellular level is of critical importance for the development of new

biomedical applications exploiting inorganic nanoparticles. However, equally important and not yet well-understood, is how the physicochemical charact Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

eristics of nanoparticles influence their interactions with complex tissues, which extend at larger scales than the cells.A typical example of such a

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

complex tissue structure is the skin. Understanding how the morphology, charge and function of nanoparticles influences their penetration through the

DOI: 10.1002/ ((please add manuscript number))Article type: Full Paper.Interactions of Skin with Gold Nanoparticles of Different Surface Charge, Shape

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_finaland, nanoparticle design rules to minimize skin penetration would be of great interest to the cosmetic industry and health and safety regulations in a

n industrial environment.2Many studies have recently targeted the subject of nanopanicle-skin interactions.12125- For example. Sonavane et al.(29) stu Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

died the penetration of 15nm, 102nm and 198nm citrate-coated gold nanoparticles through rat skin using Franz diffusion cells. Their TEM, EDS and ICP a

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

nalyses showed that the penetration of gold nanopanicles through rat skin is sizeindependent. however the 15nm gold nanoparticles showed higher permea

DOI: 10.1002/ ((please add manuscript number))Article type: Full Paper.Interactions of Skin with Gold Nanoparticles of Different Surface Charge, Shape

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_finals, result in the skin being exposed to excessive pressure and shear stress, which can affect the penetration. Krishnan et al.1301 and Filon et al.(3U

induced the penetration of citrate-coated gold nanoparticles through human skin by dermaportation using a pulsed electromagnetic field and by dermabra Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

sion, respectively. Krishnan et al.l50] concluded that 10 nm gold nanoparticles do not penetrate intact human skin; however the stratum corneum penetr

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

ation was enhanced by the pulsed electromagnetic field. On the other hand, Filon et al.1311 reported on the penetration of 12.9 nm gold nanoparticles

DOI: 10.1002/ ((please add manuscript number))Article type: Full Paper.Interactions of Skin with Gold Nanoparticles of Different Surface Charge, Shape

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_finalompared to intact skin. Huang and coworkers showed that 5nm PVP-coated gold nanoparticles are skin permeable.15 - They attributed the permeability to

the nano-bio interaction with skin lipids and the consequent induction of transient and reversible openings on the stratum corneum. Furthermore, when Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

they applied a mixture of gold nanoparticles and protein drugs, both were able to penetrate the skin barrier and migrate into the deep layers. Labouta

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

and co-workers published a number of studies on the penetration of gold nanoparticles with human skin.151221 Their data showed that 15nm citrate-coat

DOI: 10.1002/ ((please add manuscript number))Article type: Full Paper.Interactions of Skin with Gold Nanoparticles of Different Surface Charge, Shape

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_finalold nanoparticles in toluene penetrated through the stratum corneum and into viable epidermal layers of human skin. In another study by the same group

1341 the penetration of four modelgold nanoparticles (15nm citrate-coated in water, 6nm dodecanethiol-coated in toluene, 6nm 3lecithin-coated in wate Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

r and 15nm cetrimide-coated in toluene through human skin was investigated using multiphoton microscopy. They found that the correct skin exposure tim

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

e (>6h) was crucial in order to have a significant penetration extent for studying the effect of the different physicochemical, formulation and enviro

DOI: 10.1002/ ((please add manuscript number))Article type: Full Paper.Interactions of Skin with Gold Nanoparticles of Different Surface Charge, Shape

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_finalconclusions of different studies have been contradictory' as to whether nanoparticles do or do not penetrate the skin.139-401 Experimental parameters

such as skin type and condition (e.g. intact skin, and skin chemically or mechanically treated to enhance penetration), skin surface application area, Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

exposure time, skin maintenance during the experiment, application vehicle (e.g. solvent, emulsion) concentration and type of nanoparticles (chemical

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

composition, size, shape and functionality) play a key role in the evaluation of nanoparticle penetration through the skin and should be carefully co

DOI: 10.1002/ ((please add manuscript number))Article type: Full Paper.Interactions of Skin with Gold Nanoparticles of Different Surface Charge, Shape

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_finalse and human skin. Utilizing complementary characterization techniques we evaluate for the first time how the penetration of gold nanoparticles throug

h skin is influenced by the charge, morphology and function of the nanoparticles. For these experiments, we employed gold nanospheres and nanorods of Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

a well-defined size distribution and a well-understood pegylated coating as well as spherical gold nanoparticles containing cell penetration peptides.

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2. Results and Discussion2.1.Skin StructureIn general, the skin structure consists of three major layers, the epidermis (which is the top layer of the

DOI: 10.1002/ ((please add manuscript number))Article type: Full Paper.Interactions of Skin with Gold Nanoparticles of Different Surface Charge, Shape

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final we utilized two types of skin: Human skin explants from the breast area of an adult and skin from the back of neonatal mice. The choice of skin subst

rates is very important and can influence the level of penetration. Although the main skin structure is universal in mammalians, there are variations Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

to the skin characteristics related to the species and the part of the body where skin is coming from. For example, mouse skin has a markedly thinner

Revised-20manuscript-20with-20changes-20marked_dc._JDdoc_final

epidermis than human skin, but in adults has a greater number of hair follicles. The age of the subject is also critical with the skin having a higher

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