Biomimetic polydopamine loaded with janus kinase inhibitor for synergistic vitiligo therapy via hydrogel microneedles
Abstract Background Both oxidative stress and autoimmune responses play crucial roles in the development of vitiligo. Under oxidative stress, the apoptotic melanocytes expose self-antigens and release high mobility group box 1 (HMGB1), triggering autoimmune activation and recruiting CD8+ T cells. Th...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-025-03119-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832571333699960832 |
|---|---|
| author | Chunying Li Wenwen Wang Junyi Shao Sen Zhou Xiaolin Ji Youxia Xi Qiuyang Xu Yuhan Huang Jingle Wang Yilin Wan Zhiming Li |
| author_facet | Chunying Li Wenwen Wang Junyi Shao Sen Zhou Xiaolin Ji Youxia Xi Qiuyang Xu Yuhan Huang Jingle Wang Yilin Wan Zhiming Li |
| author_sort | Chunying Li |
| collection | DOAJ |
| description | Abstract Background Both oxidative stress and autoimmune responses play crucial roles in the development of vitiligo. Under oxidative stress, the apoptotic melanocytes expose self-antigens and release high mobility group box 1 (HMGB1), triggering autoimmune activation and recruiting CD8+ T cells. This process further leads to the destruction of melanocytes, resulting in the lack of melanin granules. Additionally, the accumulated CD8+ T cells release interferon-γ (IFN-γ) to activate janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in keratinocytes. Both oxidative stress and IFN-γ-JAK-STAT activation induce keratinocytes to express and release T cell chemotactic factors, exacerbating the process of vitiligo. Reducing the accumulation of CD8+ T cells by safeguarding melanocytes and keratinocytes from oxidative stress may be contemplated as a promising approach for vitiligo therapy. Results In this study, we introduce a novel therapeutic agent called PDA-JAKi, which is capable of both eliminating oxidative stress and inhibiting T cell activation. Specifically, we have incorporated the janus kinase inhibitor (JAKi) tofacitinib into antioxidant polydopamine (PDA) nanoparticles, resulting in the formation of uniform PDA-JAKi nanodrug. PDA-JAKi effectively mitigates oxidative stress-induced apoptosis in melanocytes, reducing the antigen presentation and release of HMGB1. In addition, PDA-JAKi simultaneously attenuates oxidative stress and blocks the IFN-γ-JAK-STAT pathway to reduce the expression of C-X-C motif chemokine ligand 9/10/16 (CXCL9/10/16) in keratinocytes. We precisely deliver this therapeutic agent to the dermis using microneedle (MN) patches, aiming to enhance therapeutic efficacy compared to traditional drug administration methods. After PDA-JAKi MN treatment, the symptoms of vitiligo in mice are alleviated, and the affected areas regain pigmentation. Enhancements have been observed in the dermal thickness, the numbers of melanocytes and the content of melanin within the treated skin area. Moreover, there is a notable reduction in reactive oxygen species (ROS) level. Concurrently, substantial decreases were noted in CD8+ T cell infiltration, as well as the levels of IFN-γ and chemotactic factors CXCL9/10/16. Conclusions In summary, PDA-JAKi MN patches emerge as a promising therapeutic agent for vitiligo treatment. |
| format | Article |
| id | doaj-art-cd1563d7070640379e5b34784d1e64dd |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-cd1563d7070640379e5b34784d1e64dd2025-02-02T12:41:06ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123111910.1186/s12951-025-03119-1Biomimetic polydopamine loaded with janus kinase inhibitor for synergistic vitiligo therapy via hydrogel microneedlesChunying Li0Wenwen Wang1Junyi Shao2Sen Zhou3Xiaolin Ji4Youxia Xi5Qiuyang Xu6Yuhan Huang7Jingle Wang8Yilin Wan9Zhiming Li10Department of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Medical Oncology, The Third Affiliated Hospital of Shanghai UniversityInstitute of Nano Biomedicine and Engineering, School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong UniversityDepartment of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical UniversityAbstract Background Both oxidative stress and autoimmune responses play crucial roles in the development of vitiligo. Under oxidative stress, the apoptotic melanocytes expose self-antigens and release high mobility group box 1 (HMGB1), triggering autoimmune activation and recruiting CD8+ T cells. This process further leads to the destruction of melanocytes, resulting in the lack of melanin granules. Additionally, the accumulated CD8+ T cells release interferon-γ (IFN-γ) to activate janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in keratinocytes. Both oxidative stress and IFN-γ-JAK-STAT activation induce keratinocytes to express and release T cell chemotactic factors, exacerbating the process of vitiligo. Reducing the accumulation of CD8+ T cells by safeguarding melanocytes and keratinocytes from oxidative stress may be contemplated as a promising approach for vitiligo therapy. Results In this study, we introduce a novel therapeutic agent called PDA-JAKi, which is capable of both eliminating oxidative stress and inhibiting T cell activation. Specifically, we have incorporated the janus kinase inhibitor (JAKi) tofacitinib into antioxidant polydopamine (PDA) nanoparticles, resulting in the formation of uniform PDA-JAKi nanodrug. PDA-JAKi effectively mitigates oxidative stress-induced apoptosis in melanocytes, reducing the antigen presentation and release of HMGB1. In addition, PDA-JAKi simultaneously attenuates oxidative stress and blocks the IFN-γ-JAK-STAT pathway to reduce the expression of C-X-C motif chemokine ligand 9/10/16 (CXCL9/10/16) in keratinocytes. We precisely deliver this therapeutic agent to the dermis using microneedle (MN) patches, aiming to enhance therapeutic efficacy compared to traditional drug administration methods. After PDA-JAKi MN treatment, the symptoms of vitiligo in mice are alleviated, and the affected areas regain pigmentation. Enhancements have been observed in the dermal thickness, the numbers of melanocytes and the content of melanin within the treated skin area. Moreover, there is a notable reduction in reactive oxygen species (ROS) level. Concurrently, substantial decreases were noted in CD8+ T cell infiltration, as well as the levels of IFN-γ and chemotactic factors CXCL9/10/16. Conclusions In summary, PDA-JAKi MN patches emerge as a promising therapeutic agent for vitiligo treatment.https://doi.org/10.1186/s12951-025-03119-1Oxidative stressPolydopamineJAK inhibitorMicroneedlesVitiligo |
| spellingShingle | Chunying Li Wenwen Wang Junyi Shao Sen Zhou Xiaolin Ji Youxia Xi Qiuyang Xu Yuhan Huang Jingle Wang Yilin Wan Zhiming Li Biomimetic polydopamine loaded with janus kinase inhibitor for synergistic vitiligo therapy via hydrogel microneedles Journal of Nanobiotechnology Oxidative stress Polydopamine JAK inhibitor Microneedles Vitiligo |
| title | Biomimetic polydopamine loaded with janus kinase inhibitor for synergistic vitiligo therapy via hydrogel microneedles |
| title_full | Biomimetic polydopamine loaded with janus kinase inhibitor for synergistic vitiligo therapy via hydrogel microneedles |
| title_fullStr | Biomimetic polydopamine loaded with janus kinase inhibitor for synergistic vitiligo therapy via hydrogel microneedles |
| title_full_unstemmed | Biomimetic polydopamine loaded with janus kinase inhibitor for synergistic vitiligo therapy via hydrogel microneedles |
| title_short | Biomimetic polydopamine loaded with janus kinase inhibitor for synergistic vitiligo therapy via hydrogel microneedles |
| title_sort | biomimetic polydopamine loaded with janus kinase inhibitor for synergistic vitiligo therapy via hydrogel microneedles |
| topic | Oxidative stress Polydopamine JAK inhibitor Microneedles Vitiligo |
| url | https://doi.org/10.1186/s12951-025-03119-1 |
| work_keys_str_mv | AT chunyingli biomimeticpolydopamineloadedwithjanuskinaseinhibitorforsynergisticvitiligotherapyviahydrogelmicroneedles AT wenwenwang biomimeticpolydopamineloadedwithjanuskinaseinhibitorforsynergisticvitiligotherapyviahydrogelmicroneedles AT junyishao biomimeticpolydopamineloadedwithjanuskinaseinhibitorforsynergisticvitiligotherapyviahydrogelmicroneedles AT senzhou biomimeticpolydopamineloadedwithjanuskinaseinhibitorforsynergisticvitiligotherapyviahydrogelmicroneedles AT xiaolinji biomimeticpolydopamineloadedwithjanuskinaseinhibitorforsynergisticvitiligotherapyviahydrogelmicroneedles AT youxiaxi biomimeticpolydopamineloadedwithjanuskinaseinhibitorforsynergisticvitiligotherapyviahydrogelmicroneedles AT qiuyangxu biomimeticpolydopamineloadedwithjanuskinaseinhibitorforsynergisticvitiligotherapyviahydrogelmicroneedles AT yuhanhuang biomimeticpolydopamineloadedwithjanuskinaseinhibitorforsynergisticvitiligotherapyviahydrogelmicroneedles AT jinglewang biomimeticpolydopamineloadedwithjanuskinaseinhibitorforsynergisticvitiligotherapyviahydrogelmicroneedles AT yilinwan biomimeticpolydopamineloadedwithjanuskinaseinhibitorforsynergisticvitiligotherapyviahydrogelmicroneedles AT zhimingli biomimeticpolydopamineloadedwithjanuskinaseinhibitorforsynergisticvitiligotherapyviahydrogelmicroneedles |