{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:37:26Z","timestamp":1790293046827,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["2019\/35\/O\/NZ4\/01463"],"award-info":[{"award-number":["2019\/35\/O\/NZ4\/01463"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["PL-TW\/VII\/3\/2020"],"award-info":[{"award-number":["PL-TW\/VII\/3\/2020"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005632","name":"NCBiR program","doi-asserted-by":"publisher","award":["2019\/35\/O\/NZ4\/01463"],"award-info":[{"award-number":["2019\/35\/O\/NZ4\/01463"]}],"id":[{"id":"10.13039\/501100005632","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005632","name":"NCBiR program","doi-asserted-by":"publisher","award":["PL-TW\/VII\/3\/2020"],"award-info":[{"award-number":["PL-TW\/VII\/3\/2020"]}],"id":[{"id":"10.13039\/501100005632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Psoriasis, a chronic immune-mediated skin disorder affecting over 125 million people globally, is characterized by abnormal keratinocyte proliferation and immune cell infiltration. Photodynamic therapy (PDT) remains underutilized in the treatment of psoriasis despite its potential as a promising and effective therapeutic approach. This study aimed to explore the efficacy of zinc phthalocyanine (ZnPc) and its sugar conjugates as potential antipsoriatic agents. We successfully synthesized protected and unprotected sugar-conjugated zinc phthalocyanines and evaluated their potential against cytokine-stimulated HaCaT keratinocytes, as well as an established IMQ psoriasis-like in vivo model. Tetrasubstituted protected glucose\u2013ZnPc (Glu-4-ZnPc-P) demonstrated superior phototoxicity (IC50 = 2.55 \u00b5M) compared to unprotected glucose conjugate (IC50 = 22.7 \u00b5M), protected galactose\u2013ZnPc (IC50 = 7.13 \u00b5M), and free ZnPc in cytokine-stimulated HaCaT cells (IC50 = 5.84 \u00b5M). Cellular uptake analysis revealed that IL-17A, a cytokine that plays a central role in the pathogenesis of psoriasis, enhanced unprotected Glu-4-ZnPc uptake by 56.3%, while GLUT1 inhibitor BAY-876 reduced its accumulation by 23.8%. Intracellular ROS generation following Glu-4-ZnPc-P-PDT was significantly increased after stimulation with IL-17A, correlating with in vitro photocytotoxicity. In vivo PDT using Glu-4-ZnPc-P exhibited significant improvement in Psoriasis Area and Severity Index (PASI), inhibiting splenomegaly and restoring normal skin morphology. This study highlights sugar-conjugated zinc phthalocyanines as potential candidates for targeted PDT in psoriasis, providing a basis for further clinical investigations.<\/jats:p>","DOI":"10.3390\/pharmaceutics16060838","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T05:33:28Z","timestamp":1718948008000},"page":"838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["In Vitro and In Vivo Antipsoriatic Efficacy of Protected and Unprotected Sugar\u2013Zinc Phthalocyanine Conjugates"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9904-1181","authenticated-orcid":false,"given":"Sebastian","family":"Makuch","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1264-7050","authenticated-orcid":false,"given":"Piotr","family":"Kupczyk","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7978-6330","authenticated-orcid":false,"given":"Marta","family":"Wo\u017aniak","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Makarec","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Lipi\u0144ska","sequence":"additional","affiliation":[{"name":"Experimental Animal Facility, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Klyta","sequence":"additional","affiliation":[{"name":"Experimental Animal Facility, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Sulecka-Zadka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wies\u0142aw","family":"Szeja","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariachiara","family":"Gani","sequence":"additional","affiliation":[{"name":"Department of Medicine, Laboratory of Biochemistry, P.le Kolbe 4, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Rapozzi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Laboratory of Biochemistry, P.le Kolbe 4, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Zi\u00f3\u0142kowski","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5969-6012","authenticated-orcid":false,"given":"Piotr","family":"Smole\u0144ski","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Wroc\u0142aw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"m1590","DOI":"10.1136\/bmj.m1590","article-title":"National, Regional, and Worldwide Epidemiology of Psoriasis: Systematic Analysis and Modelling Study","volume":"369","author":"Parisi","year":"2020","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1001\/jama.2020.4006","article-title":"Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA\u2014J. Am. Med. Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/nature05663","article-title":"Pathogenesis and Therapy of Psoriasis","volume":"445","author":"Lowes","year":"2007","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Rendon, A., and Sch\u00e4kel, K. (2019). Psoriasis Pathogenesis and Treatment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061475"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1111\/1346-8138.15913","article-title":"Pathophysiology of Psoriasis: A Review","volume":"48","author":"Yamanaka","year":"2021","journal-title":"J. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1016\/j.jaad.2020.02.044","article-title":"Joint American Academy of Dermatology\u2013National Psoriasis Foundation Guidelines of Care for the Management of Psoriasis with Systemic Nonbiologic Therapies","volume":"82","author":"Menter","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/j.biopha.2018.07.049","article-title":"Photodynamic Therapy\u2014Mechanisms, Photosensitizers and Combinations","volume":"106","author":"Kwiatkowski","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"24","DOI":"10.5946\/ce.2013.46.1.24","article-title":"Photodynamic Therapy (PDT): PDT Mechanisms","volume":"46","author":"Allison","year":"2013","journal-title":"Clin. Endosc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"608","DOI":"10.3389\/fchem.2021.686303","article-title":"Photodynamic Therapy for the Treatment and Diagnosis of Cancer\u2014A Review of the Current Clinical Status","volume":"9","author":"Gunaydin","year":"2021","journal-title":"Front. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3109\/09546634.2014.927816","article-title":"Photodynamic Therapy for Psoriasis","volume":"26","author":"Choi","year":"2015","journal-title":"J. Dermatol. Treat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"191","DOI":"10.6060\/mhc2012.120990w","article-title":"Practical Applications of Phthalocyanines\u2014From Dyes and Pigments to Materials for Optical, Electronic and Photo-Electronic Devices","volume":"5","author":"Schnurpfeil","year":"2012","journal-title":"Macroheterocycles"},{"key":"ref_12","unstructured":"Kadish, K.M., Smith, K.M., and Guilard, R. (2000). The Porphyrin Handbook, Elsevier."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1039\/b618478b","article-title":"Synthesis, Photophysical and Photochemical Studies of New Water-Soluble Indium(III) Phthalocyanines","volume":"6","author":"Nyokong","year":"2007","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Roguin, L.P., Chiarante, N., Garc\u00eda Vior, M.C., and Marino, J. (2019). Zinc(II) Phthalocyanines as Photosensitizers for Antitumor Photodynamic Therapy. Int. J. Biochem. Cell Biol., 114.","DOI":"10.1016\/j.biocel.2019.105575"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.colsurfb.2015.02.038","article-title":"Nanostructures of an Amphiphilic Zinc Phthalocyanine Polymer Conjugate for Photodynamic Therapy of Psoriasis","volume":"128","author":"Jin","year":"2015","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7089","DOI":"10.1002\/ejoc.201901224","article-title":"Glycoconjugated Phthalocyanines as Photosensitizers for PDT\u2014Overcoming Aggregation in Solution","volume":"2019","author":"Siemens","year":"2019","journal-title":"Eur. J. Org. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"190","DOI":"10.3389\/fchem.2022.825716","article-title":"The Surprisingly Positive Effect of Zinc-Phthalocyanines With High Photodynamic Therapy Efficacy of Melanoma Cancer","volume":"10","author":"Castro","year":"2022","journal-title":"Front. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"953","DOI":"10.3892\/ijo.2017.3854","article-title":"Novel Zinc Phthalocyanine as a Promising Photosensitizer for Photodynamic Treatment of Esophageal Cancer","volume":"50","author":"Kuzyniak","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Makuch, S., Dr\u00f3\u017cd\u017c, M., Makarec, A., Zi\u00f3\u0142kowski, P., and Wo\u017aniak, M. (2022). An Update on Photodynamic Therapy of Psoriasis\u2014Current Strategies and Nanotechnology as a Future Perspective. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179845"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1159\/000484647","article-title":"Anti-Psoriasis Effects and Mechanisms of A-(8-Quinolinoxy) Zinc Phthalocyanine-Mediated Photodynamic Therapy","volume":"44","author":"Liu","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/s41591-018-0003-0","article-title":"Differential Glucose Requirement in Skin Homeostasis and Injury Identifies a Therapeutic Target for Psoriasis Article","volume":"24","author":"Zhang","year":"2018","journal-title":"Nat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1111\/ijd.14037","article-title":"Glucose Transporter-1 (GLUT-1) Expression in Psoriasis: Correlation with Disease Severity","volume":"57","author":"Hodeib","year":"2018","journal-title":"Int. J. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1039\/b802212g","article-title":"Glycosylated Zinc(Ii) Phthalocyanines as Efficient Photosensitisers for Photodynamic Therapy. Synthesis, Photophysical Properties and in Vitro Photodynamic Activity","volume":"6","author":"Choi","year":"2008","journal-title":"Org. Biomol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9177","DOI":"10.1016\/j.tetlet.2006.10.155","article-title":"[1,2,3,4-Tetrakis(\u03b1\/\u03b2-d-Galactopyranos-6-Yl)Phthalocyaninato]Zinc(II): A Water-Soluble Phthalocyanine","volume":"47","author":"Ribeiro","year":"2006","journal-title":"Tetrahedron Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"C723","DOI":"10.1152\/ajpcell.00462.2010","article-title":"A Practical Guide to Evaluating Colocalization in Biological Microscopy","volume":"300","author":"Dunn","year":"2011","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"214626","DOI":"10.1016\/j.ccr.2022.214626","article-title":"Photochemical Properties of Phthalocyanines with Transition Metal Ions","volume":"468","author":"Wang","year":"2022","journal-title":"Coord. Chem. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Liu, J.Y., Wang, C., Zhu, C.H., Zhang, Z.H., and Xue, J.P. (2017). Preparation and In Vitro Photodynamic Activity of Glucosylated Zinc(II) Phthalocyanines as Underlying Targeting Photosensitizers. Molecules, 22.","DOI":"10.3390\/molecules22050845"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/j.1751-1097.2012.01204.x","article-title":"Fully Protected Glycosylated Zinc (II) Phthalocyanine Shows High Uptake and Photodynamic Cytotoxicity in MCF-7 Cancer Cells","volume":"89","author":"Kimani","year":"2013","journal-title":"Photochem. Photobiol."},{"key":"ref_29","first-page":"54","article-title":"The Impact of Proinflammatory Cytokines and Imiquimod on GLUT1 in HaCaT Keratinocytes\u2014A Potential Anti-Psoriatic Therapeutic Target?","volume":"57","author":"Makuch","year":"2023","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1124\/jpet.119.263657","article-title":"Glycoconjugation as a Promising Treatment Strategy for Psoriasis","volume":"373","author":"Makuch","year":"2020","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12839","DOI":"10.1039\/c3ra41647j","article-title":"A Mitochondria-Targeted Zinc(II) Phthalocyanine for Photodynamic Therapy","volume":"3","author":"Ge","year":"2013","journal-title":"RSC Adv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4496","DOI":"10.1016\/j.bmcl.2014.07.082","article-title":"Asymmetric ZnPc-Rhodamine B Conjugates for Mitochondrial Targeted Photodynamic Therapy","volume":"24","author":"Muli","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1021\/jacs.0c12330","article-title":"Nanoscale Metal-Organic Layer Isolates Phthalocyanines for Efficient Mitochondria-Targeted Photodynamic Therapy","volume":"143","author":"Nash","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e202205022","DOI":"10.1002\/slct.202205022","article-title":"Mitochondria-Targeting Phthalocyanines and Porphyrins for Enhanced Photodynamic Tumor Therapy","volume":"8","author":"Li","year":"2023","journal-title":"ChemistrySelect"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"714897","DOI":"10.3389\/fimmu.2021.714897","article-title":"Mitochondrial Reactive Oxygen Species Are Essential for the Development of Psoriatic Inflammation","volume":"12","author":"Mizuguchi","year":"2021","journal-title":"Front. Immunol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/6\/838\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:01:45Z","timestamp":1760108505000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/6\/838"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,20]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["pharmaceutics16060838"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16060838","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,20]]}}}