Linker Hydrophilicity Modulates the Anticancer Activity of RGD-Cryptophycin Conjugates
© 2020 The Authors. Published by Wiley-VCH GmbH..
Most anticancer agents are hydrophobic and can easily penetrate the tumor cell membrane by passive diffusion. This may impede the development of highly effective and tumor-selective treatment options. A hydrophilic β-glucuronidase-cleavable linker was used to connect the highly potent antimitotic agent cryptophycin-55 glycinate with the αv β3 integrin ligand c(RGDfK). Incorporation of the self-immolative linker containing glucuronic acid results in lower cytotoxicity than that of the free payload, suggesting that hydrophilic sugar linkers can preclude passive cellular uptake. In vitro drug-release studies and cytotoxicity assays demonstrated the potential of this small molecule-drug conjugate, providing guidance for the development of therapeutics containing hydrophobic anticancer drugs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Chemistry (Weinheim an der Bergstrasse, Germany) - 27(2021), 3 vom: 13. Jan., Seite 1015-1022 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Anselmi, Michele [VerfasserIn] |
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| Links: |
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| Themen: |
78VO7F77PN |
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| Anmerkungen: |
Date Completed 10.03.2021 Date Revised 10.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/chem.202003471 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM315264659 |
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| 520 | |a © 2020 The Authors. Published by Wiley-VCH GmbH. | ||
| 520 | |a Most anticancer agents are hydrophobic and can easily penetrate the tumor cell membrane by passive diffusion. This may impede the development of highly effective and tumor-selective treatment options. A hydrophilic β-glucuronidase-cleavable linker was used to connect the highly potent antimitotic agent cryptophycin-55 glycinate with the αv β3 integrin ligand c(RGDfK). Incorporation of the self-immolative linker containing glucuronic acid results in lower cytotoxicity than that of the free payload, suggesting that hydrophilic sugar linkers can preclude passive cellular uptake. In vitro drug-release studies and cytotoxicity assays demonstrated the potential of this small molecule-drug conjugate, providing guidance for the development of therapeutics containing hydrophobic anticancer drugs | ||
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| 700 | 1 | |a Kemker, Isabell |e verfasserin |4 aut | |
| 700 | 1 | |a Gentilucci, Luca |e verfasserin |4 aut | |
| 700 | 1 | |a Sewald, Norbert |e verfasserin |4 aut | |
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