Breaking the psoriasis pathological signaling cycle: A novel nanomedicine strategy targeting metabolism and oxidative stress
Psoriasis is a chronic skin disorder characterized by dysregulation of immune and epithelial cells, resulting in persistent symptoms such as erythema, scaling, and induration. The abnormal metabolism and increased oxidative stress in psoriasis lesions have been identified as key drivers in the patho...
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Elsevier
2025-06-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425004478 |
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| author | Fugen Wu Xing Xia Yuqi Han Zihao Huang Yitianhe Xu Zihao Tao Yunzhi Wang Dingchao Shen Shengnan Song Wanling Zhu Ruijie Chen Xianbao Shi Xinyu Jiang Longfa Kou |
| author_facet | Fugen Wu Xing Xia Yuqi Han Zihao Huang Yitianhe Xu Zihao Tao Yunzhi Wang Dingchao Shen Shengnan Song Wanling Zhu Ruijie Chen Xianbao Shi Xinyu Jiang Longfa Kou |
| author_sort | Fugen Wu |
| collection | DOAJ |
| description | Psoriasis is a chronic skin disorder characterized by dysregulation of immune and epithelial cells, resulting in persistent symptoms such as erythema, scaling, and induration. The abnormal metabolism and increased oxidative stress in psoriasis lesions have been identified as key drivers in the pathogenesis of psoriasis, forming a positive feedback loop within psoriatic skin. Therefore, targeting this feedback loop through modulation of local metabolism and alleviation of oxidative stress could be a rational and promising therapeutic strategy for addressing psoriasis. Herein, we designed a carrier-free nanomedicine (BTN) incorporating bilirubin (BR) and triptolide (TPL) to specifically target two key pathological features of psoriasis: inflammation induced by enhanced reactive oxygen species (ROS) and aberrant proliferation/immune activation driven by heightened nutrient metabolism. In vitro studies demonstrated that BTN effectively improved the water solubility of BR and TPL while facilitating efficient drug delivery to inflammatory keratinocytes. Mechanistically, BTN was found to alleviate the inflammatory cascade caused by oxidative stress and inhibit the IL-23/IL-17 axis. Importantly, downregulation of HIF-1α in keratinocytes resulted in blocking glucose transportation via GLUT-1 as well as amino acid transportation via LAT1, ultimately impeding excessive proliferation by disrupting nutritional requirements. In an imiquimod-induced psoriasis model, BTN effectively permeated inflamed skin epithelium with long-term retention effect. As a multifunctional nanomedicine combining ROS scavenging properties with regulation of nutrition metabolism, BTN shows great promise for reducing inflammatory cell infiltration and suppressing keratinocyte proliferation. Our findings demonstrated the great potential of BTN in ameliorating psoriasis symptoms by restoring the metabolic imbalance and mitigating oxidative stress between the epithelial and immune compartments. |
| format | Article |
| id | doaj-art-eeea89e35b5b406bbd055754222da136 |
| institution | OA Journals |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-eeea89e35b5b406bbd055754222da1362025-08-20T02:17:27ZengElsevierMaterials Today Bio2590-00642025-06-013210188710.1016/j.mtbio.2025.101887Breaking the psoriasis pathological signaling cycle: A novel nanomedicine strategy targeting metabolism and oxidative stressFugen Wu0Xing Xia1Yuqi Han2Zihao Huang3Yitianhe Xu4Zihao Tao5Yunzhi Wang6Dingchao Shen7Shengnan Song8Wanling Zhu9Ruijie Chen10Xianbao Shi11Xinyu Jiang12Longfa Kou13Department of Pediatrics, Wenling Hospital of Wenzhou Medical University, Wenling, 317500, ChinaDepartment of Pediatrics, Wenling Hospital of Wenzhou Medical University, Wenling, 317500, China; Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China; Corresponding author.Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; Corresponding author.Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; Corresponding author.Psoriasis is a chronic skin disorder characterized by dysregulation of immune and epithelial cells, resulting in persistent symptoms such as erythema, scaling, and induration. The abnormal metabolism and increased oxidative stress in psoriasis lesions have been identified as key drivers in the pathogenesis of psoriasis, forming a positive feedback loop within psoriatic skin. Therefore, targeting this feedback loop through modulation of local metabolism and alleviation of oxidative stress could be a rational and promising therapeutic strategy for addressing psoriasis. Herein, we designed a carrier-free nanomedicine (BTN) incorporating bilirubin (BR) and triptolide (TPL) to specifically target two key pathological features of psoriasis: inflammation induced by enhanced reactive oxygen species (ROS) and aberrant proliferation/immune activation driven by heightened nutrient metabolism. In vitro studies demonstrated that BTN effectively improved the water solubility of BR and TPL while facilitating efficient drug delivery to inflammatory keratinocytes. Mechanistically, BTN was found to alleviate the inflammatory cascade caused by oxidative stress and inhibit the IL-23/IL-17 axis. Importantly, downregulation of HIF-1α in keratinocytes resulted in blocking glucose transportation via GLUT-1 as well as amino acid transportation via LAT1, ultimately impeding excessive proliferation by disrupting nutritional requirements. In an imiquimod-induced psoriasis model, BTN effectively permeated inflamed skin epithelium with long-term retention effect. As a multifunctional nanomedicine combining ROS scavenging properties with regulation of nutrition metabolism, BTN shows great promise for reducing inflammatory cell infiltration and suppressing keratinocyte proliferation. Our findings demonstrated the great potential of BTN in ameliorating psoriasis symptoms by restoring the metabolic imbalance and mitigating oxidative stress between the epithelial and immune compartments.http://www.sciencedirect.com/science/article/pii/S2590006425004478BilirubinTriptolidePsoriasisNanomedicineHIF-1α |
| spellingShingle | Fugen Wu Xing Xia Yuqi Han Zihao Huang Yitianhe Xu Zihao Tao Yunzhi Wang Dingchao Shen Shengnan Song Wanling Zhu Ruijie Chen Xianbao Shi Xinyu Jiang Longfa Kou Breaking the psoriasis pathological signaling cycle: A novel nanomedicine strategy targeting metabolism and oxidative stress Materials Today Bio Bilirubin Triptolide Psoriasis Nanomedicine HIF-1α |
| title | Breaking the psoriasis pathological signaling cycle: A novel nanomedicine strategy targeting metabolism and oxidative stress |
| title_full | Breaking the psoriasis pathological signaling cycle: A novel nanomedicine strategy targeting metabolism and oxidative stress |
| title_fullStr | Breaking the psoriasis pathological signaling cycle: A novel nanomedicine strategy targeting metabolism and oxidative stress |
| title_full_unstemmed | Breaking the psoriasis pathological signaling cycle: A novel nanomedicine strategy targeting metabolism and oxidative stress |
| title_short | Breaking the psoriasis pathological signaling cycle: A novel nanomedicine strategy targeting metabolism and oxidative stress |
| title_sort | breaking the psoriasis pathological signaling cycle a novel nanomedicine strategy targeting metabolism and oxidative stress |
| topic | Bilirubin Triptolide Psoriasis Nanomedicine HIF-1α |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425004478 |
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