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Ceria Nanozyme-Integrated Microneedles Reshape the Perifollicular Microenvironment for Androgenetic Alopecia Treatment

  • Anran Yuan
    Anran Yuan
    Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
    Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
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  • , 
  • Fan Xia
    Fan Xia
    Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
    Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
    More by Fan Xia
  • , 
  • Qiong Bian
    Qiong Bian
    Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
    More by Qiong Bian
  • , 
  • Haibin Wu
    Haibin Wu
    Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
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    Orcidhttps://orcid.org/0000-0002-9043-0869
  • , 
  • Yueting Gu
    Yueting Gu
    Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
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  • , 
  • Tao Wang
    Tao Wang
    Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
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  • , 
  • Ruxuan Wang
    Ruxuan Wang
    Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
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  • , 
  • Lingling Huang
    Lingling Huang
    Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
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  • , 
  • Qiaoling Huang
    Qiaoling Huang
    Hangzhou Third People’s Hospital, Hangzhou 310009, China
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  • , 
  • Yuefeng Rao
    Yuefeng Rao
    Department of Clinical Pharmacy, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
    More by Yuefeng Rao
  • , 
  • Daishun Ling
    Daishun Ling
    Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
    Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
    More by Daishun Ling
    Orcidhttps://orcid.org/0000-0002-9977-0237
  • , 
  • Fangyuan Li*
    Fangyuan Li
    Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
    Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
    *Phone: +86-571-88208623. Email: [email protected]
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  • , and 
  • Jianqing Gao*
    Jianqing Gao
    Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
    Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
    Jiangsu Engineering Research Center for New-type External and Transdermal Preparations, Changzhou 213149, China
    *Phone: +86-571-88208436. Email: [email protected]
    More by Jianqing Gao
    Orcidhttps://orcid.org/0000-0003-1052-7060
Cite this: ACS Nano 2021, 15, 8, 13759–13769
Publication Date (Web):July 19, 2021
https://doi.org/10.1021/acsnano.1c05272
Copyright © 2021 American Chemical Society
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    Abstract

    Abstract Image

    Androgenetic alopecia (AGA) is highly prevalent in current society but lacks effective treatments. The dysregulation of the hair follicle niche induced by excessive reactive oxygen species (ROS) and insufficient vascularization in the perifollicular microenvironment is the leading cause of AGA. Herein, we designed a ceria nanozyme (CeNZ)-integrated microneedles patch (Ce-MNs) that can alleviate oxidative stress and promote angiogenesis simultaneously to reshape the perifollicular microenvironment for AGA treatment. On the basis of the excellent mechanical strength of Ce-MNs, the encapsulated CeNZs with catalase- and superoxide-mimic activities can be efficiently delivered into skin to scavenge excessive ROS. Moreover, the mechanical stimulation induced by the administration of MNs can remodel the microvasculature in the balding region. Compared with minoxidil, a widely used clinical drug for AGA treatment, Ce-MNs exhibited accelerated hair regeneration in the AGA mouse model at a lower administration frequency without inducing significant skin damage. Consequently, such a safe and perifollicular microenvironment-shaping MNs patch shows great potential for clinical AGA treatment.

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.1c05272.

    • XRD pattern, XPS analysis, TGA curves, and FT-IR spectra of hydrophobic CeNZs and DSPE-mPEG2000-modified CeNZs, TEM image, DLS analysis, and HORAC of CeNZs, preparation process scheme, release kinetics assessment, cell viability assay, ROS-scavenging activity and cellular antioxidant effect of Ce-MNs, mechanical strength evaluation of Ce-MNs and Blank-MNs, in vivo biodistribution of Ce element, photographs of mouse hair regrowth status, regenerated hair coverage and hair density on day 28, hair cycle transition assessment including the quantification of pigmented day after depilation, time profile of hair-covered area and activation of hair follicle stem cell on day 10, epidermal thickness and skin thickness evaluation, H&E staining of normal skin and Ce-MNs-treated skin, quantification of MDA on day 14 and quantification of VEGF on day 7, 14, and 21 (PDF)

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