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Topics in Current Chemistry (2020) 378:8
responsible for the observed increase in cell mortality. The degradation of AgNPs
within the cell was also considered as a source of reactive oxygen species that would
be damaging to the cell machinery and DNA [41].
Obviously, human skin would be ideal to perform in vitro skin penetration analysis. In 2012, Liu et co-workers [42] investigated the in vitro penetration and metabolic effects of 10, 30 and 60 nm citrate-capped AuNPs within viable excised human
abdominal skin after 24-h exposure. Using multiphoton tomograph-fluorescence
lifetime imaging microscopy, these authors observed penetration only into the stratum corneum, without significant penetration into the lower layers. They demonstrated that viable human skin resists permeation of small NPs, which had been previously reported to penetrate deeply in other animal skin models.
Note that a remarkable attempt to categorize the size range with its skin penetration ability was carried out by Larese Filon et al. [30] They suggested that: (1) NPs
smaller than 4 nm can both penetrate and permeate intact skin, (2) NPs in the size
range between 4 and 20 nm can permeate both intact and damaged skin, (3) NPs
with diameter between 21 and 45 nm can penetrate and permeate damaged skin, and
(4) NPs higher than 45 nm can neither penetrate nor permeate the skin. They also
considered the hydrodynamic diameter of the NPs, which is an important parameter
of the colloidal particles that can be affected greatly both in terms of ligand-coating
and the electrolyte composition of the colloidal solution [43].
2.3 Shape‑Effect
Despite the enormous literature reporting protocols for the synthesis of plasmonic
NPs with different morphologies, such as rod, triangle, bipyramid, star, cube and
others, [44–46], as well as the important effects on the resulting NP flow characteristics, with altered cell membrane interactions, macrophage uptake and circulating
lifetimes [47–49], research papers investigating the influence of the NPs shape on
skin penetration are rare (Fig. 2). This fact can be attributed mainly to the resulting higher size (e.g. > 45 nm) and to the lower resulting long-term stability of the
anisotropic NPs (i.e. non-spherical geometries). Only comparative studies between
spherical and rod-shape AuNPs can be found in the literature. A relevant study
was reported by Fernandes et al. [50], with their culture experiments in mouse and
human skin samples showing that the percentage of PEG-capped Au-nanorods (with
an aspect ratio 2.8 ± 0.5) found in all samples was higher than that obtained in similar PEG-capped spherical 15 ± 1 nm AuNPs. These results were obtained for both
positively and negatively surface charged NPs, suggesting the great influence of NPshape on penetration capacity. In the case of AgNPs, Tak and co-workers reported
a skin penetration study of differently shaped NPs using both in vitro and in vivo
models [51]. They used spherical, rod-shape and triangular AgNPs with similar
hydrodynamic diameter (~ 50 nm) and zeta-potential (+ 30 mV) to perform in vitro
analysis on ultra-thin mouse skin section by the Franz cell system, and in vivo analysis on hairless mice. In agreement with previous results for AuNPs, they showed that
rod-shaped AgNPs presented a higher permeability index than spherical and triangular AgNPs. They concluded that different shapes of AgNPs may exhibit diverse
223
Reprinted from the journal
Topics in Current Chemistry (2020) 378:8
responsible for the observed increase in cell mortality. The degradation of AgNPs
within the cell was also considered as a source of reactive oxygen species that would
be damaging to the cell machinery and DNA [41].
Obviously, human skin would be ideal to perform in vitro skin penetration analysis. In 2012, Liu et co-workers [42] investigated the in vitro penetration and metabolic effects of 10, 30 and 60 nm citrate-capped AuNPs within viable excised human
abdominal skin after 24-h exposure. Using multiphoton tomograph-fluorescence
lifetime imaging microscopy, these authors observed penetration only into the stratum corneum, without significant penetration into the lower layers. They demonstrated that viable human skin resists permeation of small NPs, which had been previously reported to penetrate deeply in other animal skin models.
Note that a remarkable attempt to categorize the size range with its skin penetration ability was carried out by Larese Filon et al. [30] They suggested that: (1) NPs
smaller than 4 nm can both penetrate and permeate intact skin, (2) NPs in the size
range between 4 and 20 nm can permeate both intact and damaged skin, (3) NPs
with diameter between 21 and 45 nm can penetrate and permeate damaged skin, and
(4) NPs higher than 45 nm can neither penetrate nor permeate the skin. They also
considered the hydrodynamic diameter of the NPs, which is an important parameter
of the colloidal particles that can be affected greatly both in terms of ligand-coating
and the electrolyte composition of the colloidal solution [43].
2.3 Shape‑Effect
Despite the enormous literature reporting protocols for the synthesis of plasmonic
NPs with different morphologies, such as rod, triangle, bipyramid, star, cube and
others, [44–46], as well as the important effects on the resulting NP flow characteristics, with altered cell membrane interactions, macrophage uptake and circulating
lifetimes [47–49], research papers investigating the influence of the NPs shape on
skin penetration are rare (Fig. 2). This fact can be attributed mainly to the resulting higher size (e.g. > 45 nm) and to the lower resulting long-term stability of the
anisotropic NPs (i.e. non-spherical geometries). Only comparative studies between
spherical and rod-shape AuNPs can be found in the literature. A relevant study
was reported by Fernandes et al. [50], with their culture experiments in mouse and
human skin samples showing that the percentage of PEG-capped Au-nanorods (with
an aspect ratio 2.8 ± 0.5) found in all samples was higher than that obtained in similar PEG-capped spherical 15 ± 1 nm AuNPs. These results were obtained for both
positively and negatively surface charged NPs, suggesting the great influence of NPshape on penetration capacity. In the case of AgNPs, Tak and co-workers reported
a skin penetration study of differently shaped NPs using both in vitro and in vivo
models [51]. They used spherical, rod-shape and triangular AgNPs with similar
hydrodynamic diameter (~ 50 nm) and zeta-potential (+ 30 mV) to perform in vitro
analysis on ultra-thin mouse skin section by the Franz cell system, and in vivo analysis on hairless mice. In agreement with previous results for AuNPs, they showed that
rod-shaped AgNPs presented a higher permeability index than spherical and triangular AgNPs. They concluded that different shapes of AgNPs may exhibit diverse
223
Reprinted from the journal