Ultrasonic delivery of silica–gold nanoshells for photothermolysis of sebaceous glands in humans: Nanotechnology from the bench to clinic

• Dilip Paithankar^a, , 1, , 
• Byeong Hee Hwang^b, 1, 2, 
• Girish Munavalli^c, 
• Arielle Kauvar^d, 
• Jenifer Lloyd^e,
• Richard Blomgren^a, 
• Linda Faupel^a, 
• Todd Meyer^a, 
• Samir Mitragotri^b, , 

 Show more

---

Abstract

Recent advances in nanotechnology have provided numerous opportunities to transform medical therapies for the treatment of diseases including cancer, atherosclerosis, and thrombosis. Here, we report, through in vitro studies and in vivo human pilot clinical studies, the use of inert, inorganic silica–gold nanoshells for the treatment of a widely prevalent and researched, yet poorly treated disease of acne. We use ~ 150 nm silica–gold nanoshells, tuned to absorb near-IR light and near-IR laser irradiation to thermally disrupt overactive sebaceous glands in the skin which define the etiology of acne-related problems. Low-frequency ultrasound was used to facilitate deep glandular penetration of the nanoshells. Upon delivery of the nanoshells into the follicles and glands, followed by wiping of superficial nanoshells from skin surface and exposure of skin to near-infrared laser, nanoshells localized in the follicles absorb light, get heated, and induce focal thermolysis of sebaceous glands. Pilot human clinical studies confirmed the efficacy of ultrasonically-delivered silica–gold nanoshells in inducing photothermal disruption of sebaceous glands without damaging collateral skin.

Naunyn Schmiedebergs Arch Pharmacol. 2014 Aug;387(8):789-93. doi: 10.1007/s00210-014-0986-0. Epub 2014 May 16.

7-Phloroeckol promotes hair growth on human follicles in vitro.

Bak SS1, Sung YK, Kim SK.

Author information

Abstract

7-Phloroeckol, phloroglucinol derivative isolated from marine brown algae, has anti-oxidative, anti-inflammatory responses and MMP inhibitory activities. In this study, we evaluated the hair growth-promoting effects of 7-phloroeckol in human hairfollicles. To investigate cell viability of human dermal papilla cells (DPCs) and outer root sheath (ORS) cells in the presence or absence of 7-phloroeckol treatment, MTT assay was employed. Moreover, gene expression and protein concentration of insulin-like growth factor (IGF)-1 was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. 7-Phloroeckol induced an increase in proliferation of DPCs and ORS cells. In addition, hair shaft growth was measured using the hair-follicle organ culture system. 7-Phloroeckol resulted in elongation of the hair shaft in cultured human hair follicles. 7-Phloroeckol induced an IGF-1 mRNA expression and protein concentration in DPCs and conditioned media, respectively. These results suggest that 7-phloroeckol promotes hair growth through stimulation of DPCs and ORS cells.

Expert Opin Ther Targets. 2014 Jul;18(7):787-806. doi: 10.1517/14728222.2014.922956. Epub 2014 May 30.

Potential targets in the discovery of new hair growth promoters for androgenic alopecia.

Jain R1, De-Eknamkul W.

Author information

Abstract

INTRODUCTION:

Androgenic alopecia (AGA) is the major type of scalp hair loss affecting 60 - 70% of the population worldwide. It is caused by two potent androgens, namely testosterone (T) and 5α-dihydrotestosterone (5α-DHT). Till date, only two FDA-approved synthetic drugs, minoxidil and finasteride, are used to cure AGA with only 35 and 48% success, respectively; therefore, a search for new drug based on the mechanism of androgens action is still needed.

AREAS COVERED:

Relevant literature was reviewed to identify current therapeutic targets and treatments for AGA. The potential targets are classified into three categories: i) 5α-reductase; ii) androgen receptor and iii) growth-factor-producing genes related to hair growth.

EXPERT OPINION:

Relevant assay systems using the right targets are required in order to obtain specific and effective drugs for AGA treatment. It is unlikely that single targeted agents will be sufficient for treating AGA, and therefore, it would be a challenge to obtain compounds with multiple activities.

KEYWORDS:

5α-reductase; IGF-1; VEGF; androgen receptor antagonist; androgen receptor translocation inhibitors; androgenic alopecia; enzyme inhibitors; fibroblast growth factor-7; growth factors inducing compounds; hepatocyte growth factor

Growth Horm IGF Res. 2014 Apr-Jun;24(2-3):89-94. doi: 10.1016/j.ghir.2014.03.004. Epub 2014 Mar 30.

Exogenous IGF-1 promotes hair growth by stimulating cell proliferation and down regulating TGF-β1 in C57BL/6 mice in vivo.

Li J1, Yang Z2, Li Z1, Gu L1, Wang Y1, Sung C3.

Author information

Abstract

OBJECTIVE:

Insulin-like growth factor 1 (IGF-1) increases the growth of cultured hair follicles and plays a role in regulatinghair migration during the development of hair follicles in transgenic mice. However, the exogenous effect of IGF-1 on hairgrowth in wild-type mice has not been reported. In the present study, we examined whether IGF-1 was an important regulator of hair follicle growth in wide-type mice in vivo.

DESIGN:

C57BL/6 mice were injected with different concentrations of IGF-1 on dorsal skin. The treated tissues were analyzed by immunoassay methods for TGF-β1 and BrdU.

RESULTS:

Local injection of IGF-1 increased hair follicle number and prolonged the growing phase during the transition from anagen to telogen. Meanwhile, immunology analyses revealed that IGF-1 also stimulated the proliferation of follicle cells in anagen of the matrix and down regulated TGF-β1 expression in hair follicles.

CONCLUSIONS:

These observations suggest that IGF-1 is an effective stimulator of hair follicle development in wide-type mice in vivo and may be a promising drug candidate for baldness therapy.

Copyright © 2014. Published by Elsevier Ltd.

J Invest Dermatol. 2015 Feb 3. doi: 10.1038/jid.2015.28. [Epub ahead of print]

Oxidative Stress-Associated Senescence in Dermal Papilla Cells of Men with Androgenetic Alopecia.

Upton JH1, Hannen RF1, Bahta AW1, Farjo N2, Farjo B2, Philpott MP1.

Author information

Abstract

Dermal papilla cells (DPCs) taken from male androgenetic alopecia (AGA) patients undergo premature senescence in vitro in association with the expression of p16INK4a, suggesting that DPCs from balding scalp are more sensitive to environmental stress than nonbalding cells. As one of the major triggers of senescence in vitro stems from the cell "culture shock" owing to oxidative stress, we have further investigated the effects of oxidative stress on balding and occipital scalp DPCs. Patient-matched DPCs from balding and occipital scalp were cultured at atmospheric (21%) or physiologically normal (2%) O2. At 21% O2, DPCs showed flattened morphology and a significant reduction in mobility, population doubling, increased levels of reactive oxygen species and senescence-associated β-Gal activity, and increased expression of p16INK4a and pRB. Balding DPCs secreted higher levels of the negative hair growth regulators transforming growth factor beta 1 and 2 in response to H2O2 but not cell culture-associated oxidative stress. Balding DPCs had higher levels of catalase and total glutathione but appear to be less able to handle oxidative stress compared with occipital DPCs. These in vitro findings suggest that there may be a role for oxidative stress in the pathogenesis of AGA both in relation to cell senescence and migration but also secretion of known hair follicle inhibitory factors.Journal of Investigative Dermatology advance online publication, 26 February 2015; doi:10.1038/jid.2015.28

Restorative effect of hair follicular dermal cells on injured human hair follicles in a mouse model.

Yamao M1, Inamatsu M, Okada T, Ogawa Y, Ishida Y, Tateno C, Yoshizato K.

Author information

Abstract

No model is available for examining whether in vivo-damaged human hair follicles (hu-HFs) are rescued by transplanting cultured hu-HF dermal cells (dermal papilla and dermal sheath cells). Such a model might be valuable for examining whether in vivo-damaged hu-HFs such as miniaturized hu-HFs in androgenic alopecia are improvable by auto-transplanting hu-HF dermal cells. In this study, we first developed mice with humanized skin composed of hu-keratinocytes and hu-dermal fibroblasts. Then, a 'humanized scalp model mouse' was generated by transplanting hu-scalp HFs into the humanized skin. To demonstrate the usability of the model, the lower halves of the hu-HFs in the model were amputated in situ, and cultured hu-HF dermal cells were injected around the amputated area. The results demonstrated that the transplanted cells contributed to the restoration of the damaged HFs. This model could be used to explore clinically effective technologies for hair restoration therapy by autologous cell transplantation.

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Red ginseng extract promotes the hair growth in cultured human hair follicles.

Park GH1, Park KY, Cho HI, Lee SM, Han JS, Won CH, Chang SE, Lee MW, Choi JH, Moon KC, Shin H, Kang YJ, Lee DH.

Author information

Abstract

Ginseng has been shown to promote hair growth in several recent studies. However, its effects on human hair follicles and its mechanisms of action have not been sufficiently elucidated. This study aimed to investigate the hair growth-promoting effects of red ginseng extract (RGE) and its ginsenosides. The proliferative activities of cultured human hair follicles treated with RGE and ginsenoside-Rb1 were assessed using Ki-67 immunostaining. Their effects on isolated human dermal papillacells (hDPCs) were evaluated using cytotoxicity assays, immunoblot analysis of signaling proteins, and the determination of associated growth factors. We examined the ability of RGE and ginsenosides to protect hair matrix keratinocyte proliferation against dihydrotestosterone (DHT)-induced suppression and their effects on the expression of androgen receptor. The in vivo hair growth-promoting effect of RGE was also investigated in C57BL/6 mice. Both RGE and ginsenoside-Rb1 enhanced the proliferation of hair matrix keratinocytes. hDPCs treated with RGE or ginsenoside-Rb1 exhibited substantial cell proliferation and the associated phosphorylation of ERK and AKT. Moreover, RGE, ginsenoside-Rb1, and ginsenoside-Rg3 abrogated the DHT-induced suppression of hair matrix keratinocyte proliferation and the DHT-induced upregulation of the mRNA expression of androgen receptor in hDPCs. Murine experiments revealed that the subcutaneous injection of 3% RGE resulted in more rapid hair growth than the negative control. In conclusion, RGE and its ginsenosides may enhance hDPC proliferation, activate ERK and AKT signaling pathways in hDPCs, upregulate hair matrix keratinocyte proliferation, and inhibit the DHT-induced androgen receptor transcription. These results suggest that red ginseng may promote hair growth in humans.

KEYWORDS:

cell growth; ginseng; ginsenosides; proliferation; signal transduction