Electric Stimulus Opens Intercellular Spaces in Skin

Hama, Susumu; Kimura, Yûki; Mikami, Aya; Shiota, Kanako; Toyoda, Mao; Tamura, Atsushi; Nagasaki, Yukio; Kanamura, Kiyoshi; Kajimoto, Kazuaki; Kogure, Kentaro

doi:10.1074/jbc.m113.514414

Cited by 33 publications

(37 citation statements)

References 31 publications

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“…7) Iontophoresis is an effective technology for transdermal delivery of nanoparticles, such as liposomes, using faint electricity. 8) We found that faint electric treatment opened intercellular junctions in the skin. 8) Further, liposomes were shown to penetrate to deep regions of the skin through the intercellular space by iontophoresis because of the flexible structure of the lipid vesicles.…”

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confidence: 83%

“…8) We found that faint electric treatment opened intercellular junctions in the skin. 8) Further, liposomes were shown to penetrate to deep regions of the skin through the intercellular space by iontophoresis because of the flexible structure of the lipid vesicles. 8) On the other hand, polymerbased nanoparticles accumulated in the epidermis due to their rigid structures.…”

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confidence: 83%

“…Accumulation of RNPs in epidermis is probably due to their rigid structures, although liposomes having flexible property penetrated to deep region of the skin through narrow intercellular space. 8) Following confirmation of the accumulation of RNPs in the epidermis upon application of the iontophoresis technique, we subsequently evaluated the protective effect of RNPs on UV-induced melanin production.…”

Section: Accumulation Of Rnps In the Epidermis By Iontophoretic Deliverymentioning

confidence: 99%

“…As stated above, RNPs selectively accumulate in the epidermis, unlike liposomes, which tend to spread to the dermis. 8) Moreover, it has been reported that TEMPO scavenges ROS catalytically. 9,10) Thus, high accumulation of RNPs in the epidermis, coupled with the ability to catalytically eliminate ROS, may improve the effects on UV-induced melanin production.…”

Section: Accumulation Of Rnps In the Epidermis By Iontophoretic Deliverymentioning

confidence: 99%

“…8) Further, liposomes were shown to penetrate to deep regions of the skin through the intercellular space by iontophoresis because of the flexible structure of the lipid vesicles. 8) On the other hand, polymerbased nanoparticles accumulated in the epidermis due to their rigid structures. 7) Thus, polymer-based nanoparticles that exhibit antioxidative activity may be useful for effective prevention of UV-mediated skin injury.…”

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confidence: 99%

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Prevention of UV-Induced Melanin Production by Accumulation of Redox Nanoparticles in the Epidermal Layer <i>via</i> Iontophoresis

Shiota

Hama

Yoshitomi

et al. 2017

Biological & Pharmaceutical Bulletin

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UV rays induce melanin production in the skin, which, from a cosmetic point of view, is problematic. Reactive oxygen species (ROS) generated in the skin upon UV irradiation are thought to be responsible for melanin production. Thus, effective antioxidants are recognized as useful tools for prevention of UV-induced melanin production. Redox nanoparticles (RNPs) containing nitroxide radicals as free radical scavengers were previously developed, and shown to be effective ROS scavengers in the body. RNPs are therefore expected to be useful for effective protection against UV-induced melanin production. However, as the sizes of RNPs are typically larger than the intercellular spaces of the skin, transdermal penetration is difficult. We recently demonstrated effective transdermal delivery and accumulation of nanoparticles in the epidermal layer via faint electric treatment, i.e., iontophoresis, suggesting that iontophoresis of RNPs may be a useful strategy for prevention of UV-induced melanin production in the skin. Herein, we performed iontophoresis of RNPs on the dorsal skin of hairless mice that produce melanin in response to light exposure. RNPs accumulated in the epidermal layer upon application of iontophoresis. Further, the combination of RNPs with iontophoresis decreased UV-induced melanin spots and melanin content in the skin. Taken together, we successfully demonstrated that iontophoresis-mediated accumulation of RNPs in the epidermis prevented melanin production.

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confidence: 83%

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confidence: 83%

Section: Accumulation Of Rnps In the Epidermis By Iontophoretic Deliverymentioning

confidence: 99%

Section: Accumulation Of Rnps In the Epidermis By Iontophoretic Deliverymentioning

confidence: 99%

mentioning

confidence: 99%

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Prevention of UV-Induced Melanin Production by Accumulation of Redox Nanoparticles in the Epidermal Layer <i>via</i> Iontophoresis

Shiota

Hama

Yoshitomi

et al. 2017

Biological & Pharmaceutical Bulletin

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Noninvasive transdermal delivery of liposomes by weak electric current

Hasan

Khatun

Fukuta

et al. 2020

Advanced Drug Delivery Reviews

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Low level electricity increases the secretion of extracellular vesicles from cultured cells

Fukuta

Nishikawa

Kogure

2020

Biochemistry and Biophysics Reports

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Exosomes, a type of extracellular vesicles, can be collected from the conditioned medium of cultured cells, and are expected to be used in disease therapy and drug delivery systems. However, since the yield of exosomes from conditioned medium is generally low, investigations to develop new methods to increase exosome secretion and to elucidate the secretion mechanism have been performed. Our previous studies demonstrated that activation of intracellular signaling including Rho GTPase and subsequent endocytosis of extraneous molecules in cells could be induced by low level electricity (0.3–0.5 mA/cm2). Since exosomes are produced in the process of endocytosis and secreted by exocytosis via certain signaling pathways, we hypothesized that low level electric treatment (ET) would increase exosome secretion from cultured cells via intracellular signaling activation. In the present study, the influence of ET (0.34 mA/cm2) on extracellular vesicle (EV) secretion from cultured cells was examined by using murine melanoma and murine fibroblast cells. The results showed that the number of EV particles collected by ultracentrifugation was remarkably increased by ET in both cell lines without cellular toxicity or changes in the particle distribution. Also, protein amounts of the collected EVs were significantly increased in both cells by ET without alteration of expression of representative exosome marker proteins. Moreover, in both cells, the ratio of particle numbers to protein amount was not significantly changed by ET. Rho GTPase inhibition significantly suppressed ET-mediated increase of EV secretion in murine melanoma, indicating that Rho GTPase activation could be involved in ET-mediated EV secretion in the cell. Additionally, there were almost no differences in uptake of each EV into each donor cell regardless of whether the cells had been exposed to ET for EV collection. Taken together, these results suggest that ET could increase EV secretion from both cancer and normal cells without apparent changes in EV quality.

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Electric Stimulus Opens Intercellular Spaces in Skin

Cited by 33 publications

References 31 publications

Prevention of UV-Induced Melanin Production by Accumulation of Redox Nanoparticles in the Epidermal Layer <i>via</i> Iontophoresis

Prevention of UV-Induced Melanin Production by Accumulation of Redox Nanoparticles in the Epidermal Layer <i>via</i> Iontophoresis

Noninvasive transdermal delivery of liposomes by weak electric current

Low level electricity increases the secretion of extracellular vesicles from cultured cells

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