Dimeric lectin chimeras as novel candidates for gb3-mediated transcytotic drug delivery through cellular barriers

Abstract: Receptor-mediated transcytosis is an elegant and promising strategy for drug delivery across biological barriers. Here, we describe a novel ligand–receptor pair based on a dimeric, engineered derivative of the Pseudomonas aeruginosa lectin LecA, here termed Di-LecA, and the host cell glycosphingolipid Gb3. We characterized the trafficking kinetics and transcytosis efficiencies in polarized Gb3-positive and -negative MDCK cells using mainly immunofluorescence in combination with confocal microscopy. To evaluate the delivery capacity of dimeric LecA chimeras, EGFP was chosen as a fluorescent model protein representing macromolecules, such as antibody fragments, and fused to either the N- or C-terminus of monomeric LecA using recombinant DNA technology. Both LecA/EGFP fusion proteins crossed cellular monolayers in vitro. Of note, the conjugate with EGFP at the N-terminus of LecA (EGFP-LecA) showed a higher release rate than the conjugate with EGFP at the C-terminus (LecA-EGFP). Based on molecular dynamics simulations and cross-linking studies of giant unilamellar vesicles, we speculate that EGFP-LecA tends to be a dimer while LecA-EGFP forms a tetramer. Overall, we confidently propose the dimeric LecA chimeras as transcytotic drug delivery tools through Gb3-positive cellular barriers for future in vivo tests

Objekt anzeigen

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Pharmaceutics. - 15, 1 (2023) , 225, ISSN: 1999-4923

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2023
• Urheber: Xu, Maokai ; Antonova, Maria ; Salavei, Pavel ; Illek, Katharina ; Meléndez Mayorga, Ana Valeria ; Omidvar, Ramin ; Thünauer, Roland ; Makshakova, Olga N. ; Römer, Winfried

Weitere Informationen

• DOI: 10.3390/pharmaceutics15010225
• URN: urn:nbn:de:bsz:25-freidok-2327668
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.