PMID- 36690435 OWN - NLM STAT- MEDLINE DCOM- 20230522 LR - 20230629 IS - 2192-2659 (Electronic) IS - 2192-2640 (Linking) VI - 12 IP - 13 DP - 2023 May TI - Glutamine-Based Metabolism Normalization and Oxidative Stress Alleviation by Self-Assembled Bilirubin/V9302 Nanoparticles for Psoriasis Treatment. PG - e2203397 LID - 10.1002/adhm.202203397 [doi] AB - Psoriasis is an immune-mediated chronic inflammatory skin disorder characterized by epidermal hyperplasia and infiltration of inflammatory cells. Even though the pathogenesis remains unclear, T helper 17 (Th17) cells-mediated inflammation and keratinocyte-involved proliferation are considered to play key roles during the occurrence and the development of psoriasis. Therefore, suppressing the infiltration/function of Th17 and the abnormal hyperplasia of keratinocytes can be a rational strategy for ameliorating and treating psoriasis. In this study, a self-assembly nanoparticle (BVn) is developed with bilirubin (an endogenous antioxidant) and V9302 (a blocker of ASCT2, an amino acid transporter mediating glutamine influx for providing energy and activating mammalian target of rapamycin [mTOR] pathway) to intervene the local metabolism and alleviate oxidative stress for psoriasis treatment. BVn effectively suppresses inflammatory keratinocyte proliferation and scavenges excess reactive oxygen species (ROS). In the in vivo psoriasis mouse model, BVn shows increased permeation and delayed retention in the psoriatic lesion and reverses the psoriasis-related symptoms, evidenced by the normalized keratinocyte condition and decreased Th17 infiltration/activation. Mechanism study indicates that BVn not only cut off the energy supply but also suppressed cell proliferation or lymph cell expansion by deactivating mTOR pathway, besides alleviated oxidative stress. BVn-based glutamine metabolism modulation strategy offers a promising strategy for psoriasis therapy. CI - (c) 2023 Wiley-VCH GmbH. FAU - Jiang, Xinyu AU - Jiang X AD - 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. AD - Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, China. FAU - Huang, Shuqi AU - Huang S AD - 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. AD - Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, China. AD - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China. FAU - Cai, Wenjing AU - Cai W AD - 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. AD - Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, China. FAU - Wang, Peiqi AU - Wang P AD - 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. FAU - Jiang, Zewei AU - Jiang Z AD - 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. FAU - Wang, Minghui AU - Wang M AD - 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. FAU - Zhang, Linyi AU - Zhang L AD - 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. FAU - Mao, Pengfei AU - Mao P AD - 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. FAU - Chen, Lijia AU - Chen L AD - 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. FAU - Wang, Ruizhen AU - Wang R AD - 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. FAU - Sun, Tuyue AU - Sun T AD - 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. FAU - Jiang, Yiling AU - Jiang Y AD - 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. FAU - Yao, Qing AU - Yao Q AD - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China. FAU - Chen, Ruijie AU - Chen R AD - 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. FAU - Kou, Longfa AU - Kou L AUID- ORCID: 0000-0001-8502-4279 AD - 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. AD - Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, China. AD - Wenzhou Key Laboratory of Basic Science and Translational Research of Radiation Oncology, Wenzhou, 325027, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230203 PL - Germany TA - Adv Healthc Mater JT - Advanced healthcare materials JID - 101581613 RN - 0RH81L854J (Glutamine) RN - RFM9X3LJ49 (Bilirubin) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Mice MH - Animals MH - Glutamine/metabolism MH - Bilirubin/metabolism MH - Hyperplasia/metabolism/pathology MH - *Psoriasis/drug therapy/metabolism/pathology MH - Keratinocytes/metabolism MH - Oxidative Stress MH - TOR Serine-Threonine Kinases/metabolism MH - *Nanoparticles MH - Mammals/metabolism OTO - NOTNLM OT - Th17 OT - V9302 OT - bilirubin OT - glutamine metabolism OT - nanoparticles OT - psoriasis EDAT- 2023/01/24 06:00 MHDA- 2023/05/22 06:42 CRDT- 2023/01/23 21:22 PHST- 2023/01/17 00:00 [received] PHST- 2023/05/22 06:42 [medline] PHST- 2023/01/24 06:00 [pubmed] PHST- 2023/01/23 21:22 [entrez] AID - 10.1002/adhm.202203397 [doi] PST - ppublish SO - Adv Healthc Mater. 2023 May;12(13):e2203397. doi: 10.1002/adhm.202203397. Epub 2023 Feb 3.