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

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 experimental anticancer agents. SynB3 cell-penetrating derivatives were applied that can cross BBB. Tuftsin to target neuropilin-1 system selectivity better tumor Moreover, SynB3-tuftsin tandem compounds synthesized combine beneficial properties peptides. showed high selective efficacy against glioblastoma cells. demonstrated superior cellular internalization. The penetration profile was determined on a lipid monolayer Transwell co-culture with noncontact HUVEC-U87 monolayers as simple ex vivo in vitro BBB models. Importantly, 3D spheroids, daunomycin-peptide possessed ability than daunomycin. These are promising tools delivery systems tunable features.