Hedenqvist, Patricia
- Department of Clinical Sciences, Swedish University of Agricultural Sciences
Abstract
Glioblastomas (GB) are the most common and deadly primary malignant brain tumors due to their infiltrative growth and resistance to conventional therapies. GB cell plasticity and differentiation into drug-resistant mesenchymal-like (MES) states protect tumors from conventional treatments. This study introduces a novel precision medicine approach employing heparin-based nanoparticles (HP-NPs) engineered to cross the blood-brain barrier and target MES-like glioma stem cells (GSCs). Encapsulating doxorubicin (DOX) in HP-NPs reduces drug-mediated complement and coagulation cascades, enhancing hemocompatibility in human whole blood. In vitro, HP-NPs demonstrate efficient uptake by patient-derived GSCs. Preclinical evaluations in patient avatars indicate plain HP-NPs outperform DOX-loaded HP-NPs in reducing GB progression. Transcriptomic studies show HP-NPs downregulate heparin-binding epidermal growth factor (HBEGF), shifting MES GSCs into less plastic astroglial-like cells, impairing tumorigenesis. HP-NPs are well-tolerated and safe at therapeutic doses in healthy rats, offering a promising new paradigm in anticancer therapy to overcome GB recurrence and improve therapeutic outcomes.
Keywords
blood-brain barrier; drug delivery; glioma stem cells; heparin; nanoparticles
Published in
Advanced Science
2025
Publisher: WILEY
SLU Authors
Manell, Elin
- Department of Clinical Sciences, Swedish University of Agricultural Sciences
- Department of Clinical Sciences, Swedish University of Agricultural Sciences
Jensen Waern, Marianne
- Department of Clinical Sciences, Swedish University of Agricultural Sciences
- Department of Clinical Sciences, Swedish University of Agricultural Sciences
UKÄ Subject classification
Nanotechnology for/in Life Science and Medicine
Cancer and Oncology
Publication identifier
- DOI: https://doi.org/10.1002/advs.202509590
Permanent link to this page (URI)
https://res.slu.se/id/publ/144694