GBM-shuttle: glioblastoma blood-brain barrier model for developing nano-shuttles

Brain tumors have a poor prognosis and are associated with a high morbidity and mortality rate in cancer patients. The blood-brain barrier (BBB) severely limits current therapeutic options, and surgical resection is only feasible for a handful of clinical scenarios. Therefore, there is an urgent need to better understand the relationship between brain tumor and brain capillaries and to develop effective therapeutics. This project aims to develop a novel glioblastoma model integrated into the blood-brain barrier in microfluidic devices and demonstrate how these systems can be used to evaluate BBB-penetrating nanoshuttles to deliver drugs to the brain to treat brain tumors. To achieve this goal, we will use cutting-edge stem cell technologies to develop a human cell- based, physiologically relevant glioblastoma BBB chip model that recapitulates tissue function and microenvironment as in vivo, eliminating many of the consequences observed in animal models and allowing us to achieve better translational outcomes for the clinic. We will search for peptides that target highly expressed proteins on brain endothelia and exhibit transcytosis activity. By developing new nano-shuttle systems coated with peptides that penetrate the BBB, we will deliver drugs to the brain at effective therapeutic concentrations while avoiding unwanted side effects.

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Funding Agency MSRT
Proje Duration
  • Start day: 1 January 2023
  • End day: 1 January 2028
Team
  • PI: Nur Mustafaoglu, Sabanci University, Turkey
  • MSc Student: Ahmet Baki Sahin, Sabanci University, Turkey
  • PhD Student: Gulin Baran, Sabanci University, Turkey
Publications
    Papers:
  • N. Cakir, H. Oncel, A. Ozkan, D. Bicak, S. Akgun Bas, N. Mustafaoglu, (2025) Developing Immunoniosomes (INs): Antibody and Fab conjugations of niosomal nanoparticles via UV-NBS and EDC/NHS chemistry for treating glioblastoma cells, International Journal of Pharmaceutics: X, 10, 100367, DOI: 10.1016/j.ijpx.2025.100367
  • G. Sevimli, E. Kus, G. Baran, M. Marashian, N. Tabatabaei, N. Mustafaoglu, (2025) Graphene nanoplatelets enhance neuronal differentiation of human bone marrow mesenchymal stem cells, Biological Research, 58, 32, DOI: 10.1186/s40659-025-00616-3
  • N. Cakir, B. Okmen Altas, G. D. Kalaycioglu, N. Mustafaoglu, N. Aydogan (2025) Development and Characterization of DHA-Integrated Nanostructured Lipid Carrier Formulations for Enhanced Cellular Binding and Uptake, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 137122, DOI: 10.1016/j.colsurfa.2025.137122
  • Y. Soliman, J. Al-khodor, G. Yildirim Koken, N. Mustafaoglu, (2024) A guide for blood–brain barrier models, FEBS Lettes, Pages: 46, DOI: 10.1002/1873-3468.15053
  • N. Cakir, N. Ozturk, A. Kara, A. Zarrabi, N. Mustafaoglu, (2024) Optimizing Niosomal Formulations for Enhanced Cellular Applications, Advances in Pharmacological and Pharmaceutical Sciences, vol. 2024, Article ID 9933465, 17 pages. DOI: 10.1155/2024/9933465
    Thesis:
  • MSc Thesis: Y. Soliman, Human bone marrow-mesenchymal stem cells differentiation into brain-like endothelial cells, 2023
  • PhD Thesis: N. Cakir, Developing Advanced Non-Invasive Nano-formulations and Drug-Conjugation Strategies against Glioblastoma via Complete Antibody and Antibody Fab Fragments, 2024
    Oral Presentations:
  • E. Aktan, A. B. Sahin, N. Mustafaoglu, Evaluating Melittin-Loaded Niosomes for Drug Delivery Across a Human Blood-Brain Barrier Model, NanoTR-19, 27-29 August 2025, Ankara, Türkiye
  • G. Baran, I. Kiris, A. B. Sahin, N. Haciormanoglu, E. G. Yilmaz, F. Inci, N. Mustafaoglu, A human cell-based 3D Glioblastoma-BBB-on-a-Chip Model for Studying Tumor Microenvironment, FEBS Young Scientist Forum, 5-9 July, 2025, Sapanca, Türkiye
    Poster Presentations:
  • G. Baran, I. Kiris, A. B. Sahin, N. Haciormanoglu, E. G. Yilmaz, F. Inci, N. Mustafaoglu, A Humanized 3D Glioblastoma Disease Model to Research Glioblastoma-Derived Extracellular Vesicles, Nanomed Europe 2025 (NME25), 27-30 May 2025, Barcelona, Spain
  • A. B. Sahin, G. Baran, N. Mustafaoglu, Assessing melittin modified niosomes on a human BBB-on-a-chip model for drug delivery purposes, Nanomed Europe 2025 (NME25), 27-30 May 2025, Barcelona, Spain
  • G. Baran, I. Kiris, A. B. Sahin, N. Haciormanoglu, E. G. Yilmaz, F. Inci, N. Mustafaoglu, A Physiologically Relevant Glioblastoma Tumor Microenvironment Model to Investigate the Role of Extracellular Vesicles on Disease Progression and Treatment, Extracellular Vesicles Conference - 2024, 20-21 September 2024, Ankara, Türkiye
  • A. B. Sahin, A. E. Aktan, U. P. Elexpe, N. Cakir, N. Mustafaoglu, Development and characterization of melittin-modified niosomes, 9th Internatinal Congress of the Molecular Biology Association of Turkey, 12-14 September 2024, Izmir, Türkiye
  • G. Baran, N. Mustafaoglu, A Human Cell-Based 3D In Vitro Glioblastoma Microfluidic Model Integrated With Blood-Brain-Barrier Functionality, 9th Internatinal Congress of the Molecular Biology Association of Turkey, 12-14 September 2024, Izmir, Türkiye
  • A. B. Sahin, A. E. Aktan, Y. Z. Sensan, N. Cakir, N. Mustafaoglu, Melittin-Enhanced Niosomes: Design, Characterization, and in vitro Applications, NanoTR-18: 18th Nanoscience and Nanotechnology Conference, 26-28 August 2024, Istanbul, Türkiye
  • G. Baran, N. Mustafaoglu, Glioblastoma-Blood-Brain-Barrier-on-a-chip, 5th International Eurasia Biochemical Approaches and Technologies Congress, 02-05 November 2023, Antalya, Turkiye
  • Y. Soliman, G. Baran, N. Mustafaoglu, Human Bone Marrow-Mesenchymal Stem Cells Differentiation into Brain-Like Endothelial Cells, 5th International Eurasia Biochemical Approaches and Technologies Congress, 02-05 November 2023, Antalya, Turkiye
  • N. Cakir, E. D. Daglikoca, D. Karabulut, S. Akgun, Y. Capan, N. Mustafaoglu, Designing and Characterization of Antibody and Fab fragment conjugated Niosomal nanoparticles, 8th European Congress on Advanced Nanotechnology and Nanomaterials, 12-12 October 2023, London, UK
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