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.
- MeSH
- antitumorózní látky chemie farmakokinetika farmakologie MeSH
- buněčné sféroidy účinky léků metabolismus MeSH
- endoteliální buňky pupečníkové žíly (lidské) MeSH
- glioblastom farmakoterapie metabolismus MeSH
- hematoencefalická bariéra metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádorové buňky kultivované MeSH
- nádory mozku farmakoterapie metabolismus MeSH
- neuropilin-1 metabolismus MeSH
- nosiče léků chemie farmakokinetika farmakologie MeSH
- oligopeptidy chemie farmakokinetika farmakologie MeSH
- penetrační peptidy chemie farmakokinetika farmakologie MeSH
- systémy cílené aplikace léků MeSH
- tuftsin analogy a deriváty farmakokinetika farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
