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ACS Nano, Publication Date (Web): June 27, 2018 | DOI: 10.1021/acsnano.8b02330 Nanoparticle-Assisted Transcutaneous Delivery of a Signal Transducer and Activator of Transcription 3-Inhibiting Peptide Ameliorates Psoriasis-like Skin Inflammation

Jin Yong Kim^†⊥ , Jinhyo Ahn^§∥ , Jinjoo Kim^‡ , Minsuk Choi^‡ , Hyungsu Jeon^‡ , Kibaek Choe^§∥ , Dong Yun Lee^†# , Pilhan Kim^§∥ , and Sangyong Jon^*†‡^†Graduate School of Medical Science and Engineering, ^‡KAIST Institute for the BioCentury, Department of Biological Sciences, ^§Graduate School of Nanoscience and Technology, and ^∥KAIST Institute for Health Science and Technology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea

^⊥Division of Gastroenterology, Department of Internal Medicine and ^#Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
^*Corresponding Author

Abstract

Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in psoriatic skin inflammation and acts as a key player in the pathogenesis and progression of this autoimmune disease. Although numerous inhibitors that intervene in STAT3-associated pathways have been tested, an effective, highly specific inhibitor of STAT3 has yet to be identified. Here, we evaluated the in vitro and in vivo biological activity and therapeutic efficacy of a high-affinity peptide specific for STAT3 (APTstat3) after topical treatment via intradermal and transcutaneous delivery. Using a preclinical model of psoriasis, we show that intradermal injection of APTstat3 tagged with a 9-arginine cell-penetrating peptide (APTstat3-9R) reduced disease progression and modulated psoriasis-related cytokine signaling through inhibition of STAT3 phosphorylation. Furthermore, by complexing APTstat3-9R with specific lipid formulations led to formation of discoidal lipid nanoparticles (DLNPs), we were able to achieve efficient skin penetration of the STAT3-inhibiting peptide after transcutaneous administration, thereby effectively inhibiting psoriatic skin inflammation. Collectively, these findings suggest that DLNP-assisted transcutaneous delivery of a STAT3-inhibiting peptide could be a promising strategy for treating psoriatic skin inflammation without causing adverse systemic events. Moreover, the DLNP system could be used for transdermal delivery of other therapeutic peptides.

Keywords: aptides; cell-penetrating peptide; lipid nanoparticles; psoriasis; signal transducer and activator of transcription 3; transdermal delivery

논문정보

형식Research article
게재일2018년 06월 (BRIC 등록일 2018-07-04)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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