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- Title
Linker Hydrophilicity Modulates the Anticancer Activity of RGD–Cryptophycin Conjugates.
- Authors
Anselmi, Michele; Borbély, Adina; Figueras, Eduard; Michalek, Carmela; Kemker, Isabell; Gentilucci, Luca; Sewald, Norbert
- Abstract
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 αvβ3 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.
- Subjects
ANTIMITOTIC agents; ANTINEOPLASTIC agents; GLUCURONIC acid; CELL membranes; INTEGRINS; SMALL molecules
- Publication
Chemistry - A European Journal, 2021, Vol 27, Issue 3, p1015
- ISSN
0947-6539
- Publication type
Academic Journal
- DOI
10.1002/chem.202003471