Topical transdermal administration of lenalidomide nanosuspensions-based hydrogels against melanoma: In vitro and in vivo studies
Percutaneous neoadjuvant therapy has proven effective in diminishing tumor size and the surgical intervention area, which couldeffectively mitigate the risk of tumor recurrence and enhance immunotherapy efficacy. Lenalidomide, an approved medication orally used to treat myeloma, was loaded into nano...
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| Language: | English |
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Elsevier
2025-06-01
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| Series: | International Journal of Pharmaceutics: X |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590156725000015 |
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| author | Mengdi Zhang Haiying Qiu Zheyi Han Yazhong Ma Jingjing Hou Jingwei Yuan Haiyan Jia Menglu Zhou Hongjie Lu Yan Wu |
| author_facet | Mengdi Zhang Haiying Qiu Zheyi Han Yazhong Ma Jingjing Hou Jingwei Yuan Haiyan Jia Menglu Zhou Hongjie Lu Yan Wu |
| author_sort | Mengdi Zhang |
| collection | DOAJ |
| description | Percutaneous neoadjuvant therapy has proven effective in diminishing tumor size and the surgical intervention area, which couldeffectively mitigate the risk of tumor recurrence and enhance immunotherapy efficacy. Lenalidomide, an approved medication orally used to treat myeloma, was loaded into nanosuspensions-based hydrogels (Len-NBHs) for transdermal administration as a percutaneous neoadjuvant therapy. This study was designed to investigate the inhibitory effect and mechanism of Len-NBHs on melanoma. Network pharmacology and transcriptomic analyses identified key targets and signaling pathways. The effects of lenalidomide on melanoma were further verified through Western blotting, immunohistochemistry, immunofluorescence, and quantitative real-time polymerase chain reaction，using both in vitro cell experiments and in vivo melanoma mouse models. Lenalidomide could induce melanoma cells apoptosis, disrupt cell cycle progression, impede cell migration and invasion, and modify tumor microenvironment (TME). Mechanistically, lenalidomide reversed the abnormal activation of the PI3K-AKT signaling pathway and the overexpression of CD93, while also recruiting CD8+ T cells, CD4+ T cells, and dendritic cells to infiltrate the tumor site. Transdermal administration of Len-NBHs represents a promising adjuvant therapy for the treatment of malignant melanoma. Preoperative administration of Len-NBHs can inhibit the outward spread of melanoma, reduce tumor size, thereby decreasing the surgical excision area and improving patient survival rates and prognosis. |
| format | Article |
| id | doaj-art-ad82ddef09bd4023ad1987e21886cc99 |
| institution | Kabale University |
| issn | 2590-1567 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Pharmaceutics: X |
| spelling | doaj-art-ad82ddef09bd4023ad1987e21886cc992025-01-19T06:26:35ZengElsevierInternational Journal of Pharmaceutics: X2590-15672025-06-019100316Topical transdermal administration of lenalidomide nanosuspensions-based hydrogels against melanoma: In vitro and in vivo studiesMengdi Zhang0Haiying Qiu1Zheyi Han2Yazhong Ma3Jingjing Hou4Jingwei Yuan5Haiyan Jia6Menglu Zhou7Hongjie Lu8Yan Wu9Air Force Medical Center, PLA, Air Force Medical University, Beijing, China.Air Force Medical Center, PLA, Air Force Medical University, Beijing, China.Air Force Medical Center, PLA, Air Force Medical University, Beijing, China.Air Force Medical Center, PLA, Air Force Medical University, Beijing, China.Air Force Medical Center, PLA, Air Force Medical University, Beijing, China.Air Force Medical Center, PLA, Air Force Medical University, Beijing, China.Air Force Medical Center, PLA, Air Force Medical University, Beijing, China.Air Force Medical Center, PLA, Air Force Medical University, Beijing, China.Air Force Medical Center, PLA, Air Force Medical University, Beijing, China.Corresponding author at: Air Force Medical Center, PLA., No.30 Fucheng Road, Haidian District, Beijing 100142, China.; Air Force Medical Center, PLA, Air Force Medical University, Beijing, China.Percutaneous neoadjuvant therapy has proven effective in diminishing tumor size and the surgical intervention area, which couldeffectively mitigate the risk of tumor recurrence and enhance immunotherapy efficacy. Lenalidomide, an approved medication orally used to treat myeloma, was loaded into nanosuspensions-based hydrogels (Len-NBHs) for transdermal administration as a percutaneous neoadjuvant therapy. This study was designed to investigate the inhibitory effect and mechanism of Len-NBHs on melanoma. Network pharmacology and transcriptomic analyses identified key targets and signaling pathways. The effects of lenalidomide on melanoma were further verified through Western blotting, immunohistochemistry, immunofluorescence, and quantitative real-time polymerase chain reaction，using both in vitro cell experiments and in vivo melanoma mouse models. Lenalidomide could induce melanoma cells apoptosis, disrupt cell cycle progression, impede cell migration and invasion, and modify tumor microenvironment (TME). Mechanistically, lenalidomide reversed the abnormal activation of the PI3K-AKT signaling pathway and the overexpression of CD93, while also recruiting CD8+ T cells, CD4+ T cells, and dendritic cells to infiltrate the tumor site. Transdermal administration of Len-NBHs represents a promising adjuvant therapy for the treatment of malignant melanoma. Preoperative administration of Len-NBHs can inhibit the outward spread of melanoma, reduce tumor size, thereby decreasing the surgical excision area and improving patient survival rates and prognosis.http://www.sciencedirect.com/science/article/pii/S2590156725000015Lenalidomide nanosuspensions-based hydrogelsTransdermal administrationMelanoma TranscriptomicImmunoregulation |
| spellingShingle | Mengdi Zhang Haiying Qiu Zheyi Han Yazhong Ma Jingjing Hou Jingwei Yuan Haiyan Jia Menglu Zhou Hongjie Lu Yan Wu Topical transdermal administration of lenalidomide nanosuspensions-based hydrogels against melanoma: In vitro and in vivo studies International Journal of Pharmaceutics: X Lenalidomide nanosuspensions-based hydrogels Transdermal administration Melanoma Transcriptomic Immunoregulation |
| title | Topical transdermal administration of lenalidomide nanosuspensions-based hydrogels against melanoma: In vitro and in vivo studies |
| title_full | Topical transdermal administration of lenalidomide nanosuspensions-based hydrogels against melanoma: In vitro and in vivo studies |
| title_fullStr | Topical transdermal administration of lenalidomide nanosuspensions-based hydrogels against melanoma: In vitro and in vivo studies |
| title_full_unstemmed | Topical transdermal administration of lenalidomide nanosuspensions-based hydrogels against melanoma: In vitro and in vivo studies |
| title_short | Topical transdermal administration of lenalidomide nanosuspensions-based hydrogels against melanoma: In vitro and in vivo studies |
| title_sort | topical transdermal administration of lenalidomide nanosuspensions based hydrogels against melanoma in vitro and in vivo studies |
| topic | Lenalidomide nanosuspensions-based hydrogels Transdermal administration Melanoma Transcriptomic Immunoregulation |
| url | http://www.sciencedirect.com/science/article/pii/S2590156725000015 |
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