دورية أكاديمية
E-selectin binding peptide-polymer-drug conjugates and their selective cytotoxicity against vascular endothelial cells.
| العنوان: | E-selectin binding peptide-polymer-drug conjugates and their selective cytotoxicity against vascular endothelial cells. |
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| المؤلفون: | Shamay Y; Department of Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel., Paulin D, Ashkenasy G, David A |
| المصدر: | Biomaterials [Biomaterials] 2009 Nov; Vol. 30 (32), pp. 6460-8. Date of Electronic Publication: 2009 Aug 28. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 8100316 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-5905 (Electronic) Linking ISSN: 01429612 NLM ISO Abbreviation: Biomaterials Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <1995-> : Amsterdam : Elsevier Science Original Publication: [Guilford, England] : IPC Science and Technology Press, 1980- |
| مواضيع طبية MeSH: | Acrylamides/*administration & dosage , Acrylamides/*chemistry , Doxorubicin/*administration & dosage , Doxorubicin/*chemistry , Drug Carriers/*chemistry , E-Selectin/*chemistry , E-Selectin/*pharmacology , Endothelial Cells/*drug effects , Endothelial Cells/*physiology , Galactosamine/*administration & dosage , Galactosamine/*chemistry, Apoptosis/drug effects ; Cell Line ; Cell Survival/drug effects ; HL-60 Cells ; Humans ; Materials Testing |
| مستخلص: | The hypothesis that E-selectin on activated endothelial cells could be exploited to selectively target drug delivery systems to tumor vasculature was investigated. HPMA copolymer-doxorubicin (DOX) conjugates displaying the high affinity E-selectin binding peptide (Esbp, primary sequence DITWDQLWDLMK) as targeting ligand were synthesized and tested for their cytotoxicity and intracellular fate in human immortalized vascular endothelial cells (IVECs). The targeted copolymers displaying multiple copies of Esbp are bound to surface-associated E-selectin with affinity at the low nano-molar range, three orders of magnitude stronger than the free Esbp. In addition, the binding affinity of the HPMA-Esbp copolymers to E-selectin expressing IVECs was found to be 10-fold superior relative to non-targeted copolymers. Once bound, E-selectin facilitated rapid internalization and lysosomal trafficking of the copolymers. This lysosomotropism of HPMA-Esbp-bound DOX copolymers was then correlated with a 150-fold higher cytotoxicity relative to non-targeted HPMA-DOX conjugates. These findings strongly support the emerging role of E-selectin as a viable target for controlled drug delivery in cancer therapy. |
| المشرفين على المادة: | 0 (Acrylamides) 0 (Drug Carriers) 0 (E-Selectin) 0 (HPMA coploymer-doxorubicin-galactosamine) 7535-00-4 (Galactosamine) 80168379AG (Doxorubicin) |
| تواريخ الأحداث: | Date Created: 20090901 Date Completed: 20091201 Latest Revision: 20131121 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.biomaterials.2009.08.013 |
| PMID: | 19716600 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1878-5905 |
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| DOI: | 10.1016/j.biomaterials.2009.08.013 |