Preparation and <i>In Vitro</i> Validation of a Cucurbit[7]uril-Peptide Conjugate Targeting the LDL Receptor
Xue Yang, Karine Varini, Magali Godard, Fanny Gassiot, Rose Sonnette, Géraldine Ferracci, Belinda Pecqueux, Valérie Monnier, Laurence Charles, Sébastien Maria, Micaël Hardy, Olivier Ouari, Michel Khrestchatisky, Pascaline Lécorché, Guillaume Jacquot, David Bardelang
Abstract
to cucurbit[7]uril (CB[7]) to develop a new kind of drug delivery system (DDS), namely, CB[7]-VH4127, with maintained binding affinity to the LDLR. To evaluate the uptake potential of this bismacrocyclic compound, another conjugate was prepared comprising a high-affinity group for CB[7] (adamantyl(Ada)-amine) coupled to the fluorescent tracker Alexa680 (A680). The resulting A680-Ada·CB[7]-VH4127 supramolecular complex demonstrated conserved LDLR-binding potential and improved LDLR-mediated endocytosis and intracellular accumulation potential in LDLR-expressing cells. The combination of two technologies, namely, monofunctionalized CB[7] and the VH4127 LDLR-targeting peptide, opens new avenues in terms of targeting and intracellular delivery to LDLR-expressing tissues or tumors. The versatile transport capacity of CB[7], known to bind a large spectrum of bioactive or functional compounds, makes this new DDS suitable for a wide range of therapeutic or imaging applications.