دورية أكاديمية
The effect of subcellular localization on the efficiency of EGFR-targeted VHH photosensitizer conjugates.
| العنوان: | The effect of subcellular localization on the efficiency of EGFR-targeted VHH photosensitizer conjugates. |
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| المؤلفون: | van Lith SAM; Department of Pathology, Radboudumc, Geert Grooteplein zuid 10, 6525 GA Nijmegen, The Netherlands., van den Brand D; Department of Biochemistry, Radboudumc, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands; Department of Obstetrics and Gynaecology, Radboudumc, Geert Grooteplein zuid 10, 6525 GA Nijmegen, The Netherlands., Wallbrecher R; Department of Biochemistry, Radboudumc, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands., Wübbeke L; Department of Pathology, Radboudumc, Geert Grooteplein zuid 10, 6525 GA Nijmegen, The Netherlands., van Duijnhoven SMJ; Department of Pathology, Radboudumc, Geert Grooteplein zuid 10, 6525 GA Nijmegen, The Netherlands., Mäkinen PI; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, Kuopio, Finland., Hoogstad-van Evert JS; Department of Obstetrics and Gynaecology, Radboudumc, Geert Grooteplein zuid 10, 6525 GA Nijmegen, The Netherlands., Massuger L; Department of Obstetrics and Gynaecology, Radboudumc, Geert Grooteplein zuid 10, 6525 GA Nijmegen, The Netherlands., Ylä-Herttuala S; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, Kuopio, Finland; Heart Center, Kuopio University Hospital, 70211 Kuopio, Finland., Brock R; Department of Biochemistry, Radboudumc, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands., Leenders WPJ; Department of Pathology, Radboudumc, Geert Grooteplein zuid 10, 6525 GA Nijmegen, The Netherlands; Department of Biochemistry, Radboudumc, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands. Electronic address: William.Leenders@radboudumc.nl. |
| المصدر: | European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2018 Mar; Vol. 124, pp. 63-72. Date of Electronic Publication: 2017 Dec 20. |
| نوع المنشور: | Comparative Study; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 9109778 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3441 (Electronic) Linking ISSN: 09396411 NLM ISO Abbreviation: Eur J Pharm Biopharm Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Science Original Publication: Stuttgart : Wissenschaftliche Verlagsgesellschaft, c1991- |
| مواضيع طبية MeSH: | ErbB Receptors/*metabolism , Immunoconjugates/*pharmacology , Ovarian Neoplasms/*drug therapy , Photochemotherapy/*methods , Photosensitizing Agents/*pharmacology , Single-Domain Antibodies/*metabolism, Cell Death/drug effects ; Cell Line, Tumor ; Cell-Penetrating Peptides/chemistry ; Cell-Penetrating Peptides/metabolism ; Dose-Response Relationship, Drug ; Drug Compounding ; Endocytosis ; ErbB Receptors/immunology ; Female ; Humans ; Immunoconjugates/chemistry ; Immunoconjugates/immunology ; Immunoconjugates/metabolism ; Nanomedicine/methods ; Ovarian Neoplasms/immunology ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Photosensitizing Agents/chemistry ; Photosensitizing Agents/metabolism ; Single-Domain Antibodies/chemistry ; Single-Domain Antibodies/immunology ; Technology, Pharmaceutical/methods |
| مستخلص: | Photodynamic therapy (PDT) is an emerging method to treat light-accessible malignancies. To increase specificity and allow dose reduction, conjugates of photosensitizers (PS) with antibodies against tumor-associated antigens have been developed for photoimmunotherapy (PIT). However, so far it is unclear whether cellular internalization of these conjugates after binding affects PIT efficacy. The use of low molecular weight llama single domain antibodies (VHHs, nanobodies) for PIT is preferred above full size antibodies because of better tumor penetration. Therefore, we functionalized the VHH 7D12, directed against the epidermal growth factor receptor (EGFR), with a PS (IRDye700DX). To assess the impact of cellular internalization on activity, the VHHs were additionally conjugated to a cell-penetrating peptide (VHH [PS] -CPP). Here we show that upon illumination with near-infrared (NIR) light, both VHH [PS] and VHH [PS] -CPP conjugates specifically induce cell death of EGFR expressing cancer cell lines and of EGFR-expressing cells derived from surgically obtained ascites from patients with high-grade serous ovarian cancer. However, VHH [PS] conjugates were significantly more effective compared to internalizing VHH [PS] -CPP suggesting that cell surface association is required for optimal therapeutic activity. (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Cell-penetrating peptide; EGFR; Nanobody/VHH; Ovarian cancer; Photodynamic therapy; Site specific conjugation |
| المشرفين على المادة: | 0 (Cell-Penetrating Peptides) 0 (Immunoconjugates) 0 (Photosensitizing Agents) 0 (Single-Domain Antibodies) EC 2.7.10.1 (EGFR protein, human) EC 2.7.10.1 (ErbB Receptors) |
| تواريخ الأحداث: | Date Created: 20171224 Date Completed: 20180831 Latest Revision: 20181202 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.ejpb.2017.12.009 |
| PMID: | 29274374 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-3441 |
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| DOI: | 10.1016/j.ejpb.2017.12.009 |