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Updated: Nov 12, 2025
A 3D Spheroid Model for Glioblastoma
Published on: April 9, 2020
Cellular Internalization and Inhibition Capacity of New Anti-Glioma Peptide Conjugates: Physicochemical
Zsuzsa Baranyai1, Beáta Biri-Kovács1,2, Martin Krátký3
1Eötvös Loránd Research Network, Research Group of Peptide Chemistry, Eötvös Loránd University, Pázmány Péter Sétány 1/A, H-1117 Budapest, Hungary.
Abstract:
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.
Insights
New peptide conjugates overcome the blood-brain barrier (BBB) and enhance drug delivery for brain cancer treatment. These novel compounds show high efficacy and tumor penetration, offering promising therapeutic potential.
Area of Science:
- Biochemistry
- Nanotechnology
- Oncology
Background:
- Therapeutic agents for brain malignancies struggle with blood-brain barrier (BBB) transport and poor tumor penetration.
- Developing effective drug delivery systems for brain cancers remains a significant challenge.
Purpose of the Study:
- To engineer peptide conjugates capable of crossing the BBB and improving anticancer agent delivery to brain tumors.
- To synthesize and evaluate SynB3-tuftsin tandem compounds for enhanced BBB penetration and tumor targeting.
Main Methods:
- Development of peptide conjugates using SynB3 and tuftsin derivatives.
- Assessment of cellular internalization and cytotoxicity against glioblastoma cells.
- Evaluation of BBB penetration using lipid monolayer and Transwell co-culture models.
- Analysis of tumor penetration in 3D spheroids.
Main Results:
- Most peptide conjugates exhibited high and selective efficacy against glioblastoma cells.
- SynB3 and tandem derivatives showed superior cellular uptake and internalization.
- Daunomycin-peptide conjugates demonstrated improved tumor penetration in 3D spheroids compared to daunomycin alone.
Conclusions:
- Peptide conjugates offer a promising strategy to overcome BBB limitations for brain cancer therapy.
- SynB3-tuftsin tandem compounds possess tunable features for optimized drug delivery systems.
- These conjugates represent a significant advancement in developing targeted therapies for brain malignancies.
