Cellular Internalization and Inhibition Capacity of New Anti-Glioma Peptide Conjugates: Physicochemical Characterization and Evaluation on Various Monolayer- and 3D-Spheroid-Based in Vitro Platforms.

Autor: Baranyai Z; Eötvös Loránd Research Network, Research Group of Peptide Chemistry, Eötvös Loránd University, Pázmány Péter Sétány 1/A, H-1117 Budapest, Hungary., Biri-Kovács B; Eötvös Loránd Research Network, Research Group of Peptide Chemistry, Eötvös Loránd University, Pázmány Péter Sétány 1/A, H-1117 Budapest, Hungary.; Institute of Chemistry, Eötvös Loránd University, Pázmány Péter Sétány 1/A, H-1117 Budapest, Hungary., Krátký M; Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic., Szeder B; Institute of Enzymology, Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, H-1117 Budapest, Hungary., Debreczeni ML; 3rd Department of Medicine Research Laboratory, Semmelweis University, Kútvölgyi út 4, H-1125 Budapest, Hungary., Budai J; Eötvös Loránd Research Network, Research Group of Peptide Chemistry, Eötvös Loránd University, Pázmány Péter Sétány 1/A, H-1117 Budapest, Hungary., Kovács B; Centre for Ecological Research, Institute of Ecology and Botany, Alkotmány u. 2-4, H-2163 Vácrátót, Hungary., Horváth L; Eötvös Loránd Research Network, Research Group of Peptide Chemistry, Eötvös Loránd University, Pázmány Péter Sétány 1/A, H-1117 Budapest, Hungary., Pári E; Laboratory of Interfaces and Nanostructures, Institute of Chemistry, Eötvös Loránd University, Pázmány Péter Sétány 1/A, H-1117 Budapest, Hungary., Németh Z; 3rd Department of Medicine Research Laboratory, Semmelweis University, Kútvölgyi út 4, H-1125 Budapest, Hungary., Cervenak L; 3rd Department of Medicine Research Laboratory, Semmelweis University, Kútvölgyi út 4, H-1125 Budapest, Hungary., Zsila F; Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, H-1117 Budapest, Hungary., Méhes E; Department of Biological Physics, Institute of Physics, Eötvös Loránd University, Pázmány Péter Sétány 1/A, H-1117 Budapest, Hungary., Kiss É; Laboratory of Interfaces and Nanostructures, Institute of Chemistry, Eötvös Loránd University, Pázmány Péter Sétány 1/A, H-1117 Budapest, Hungary., Vinšová J; Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic., Bősze S; Eötvös Loránd Research Network, Research Group of Peptide Chemistry, Eötvös Loránd University, Pázmány Péter Sétány 1/A, H-1117 Budapest, Hungary.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2021 Mar 25; Vol. 64 (6), pp. 2982-3005. Date of Electronic Publication: 2021 Mar 15.
DOI: 10.1021/acs.jmedchem.0c01399
Abstrakt: Most therapeutic agents used for treating brain malignancies face hindered transport through the blood-brain barrier (BBB) and poor tissue penetration. To overcome these problems, we developed peptide conjugates of conventional and experimental anticancer agents. SynB3 cell-penetrating peptide derivatives were applied that can cross the BBB. Tuftsin derivatives were used to target the neuropilin-1 transport system for selectivity and better tumor penetration. Moreover, SynB3-tuftsin tandem compounds were synthesized to combine the beneficial properties of these peptides. Most of the conjugates showed high and selective efficacy against glioblastoma cells. SynB3 and tandem derivatives demonstrated superior cellular internalization. The penetration profile of the conjugates was determined on a lipid monolayer and Transwell co-culture system with noncontact HUVEC-U87 monolayers as simple ex vivo and in vitro BBB models. Importantly, in 3D spheroids, daunomycin-peptide conjugates possessed a better tumor penetration ability than daunomycin. These conjugates are promising tools for the delivery systems with tunable features.
Databáze: MEDLINE
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