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journal article·2026-01Open access

Therapeutic Reprogramming of Glioblastoma Phenotypic States Using Multifunctional Heparin Nanoparticles

Vadim Le Joncour, Austin D. Evans, Camilla Karoliina Bergström, Vignesh Kumar Rangasami, Sumanta Samanta, Nithiyanandan Krishnan, Yuji Teramura, Bo Nilsson, Patricia Hedenqvist, Elin Manell, Jons Hilborn, Marianne‐Jensen Waern, Oommen P. Varghese, Pirjo Laakkonen, Oommen P. Oommen

Advanced Science· Volume 13· Issue 3
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Source abstract

Abstract

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.
Source: crossref · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Cancer Cells and Metastasis · Nanoparticle-Based Drug Delivery · Proteoglycans and glycosaminoglycans research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Neuroscience Center Helsinki Institute of Life Science and iCAN Digital Precision Medicine Flagship Program University of Helsinki Haartmaninkatu 8 Helsinki 00290 Finland

Bioengineering and Nanomedicine Lab Faculty of Medicine and Health Technology Tampere University Korkeakoulunkatu 3 Tampere 33720 Finland

Department of Bioengineering Phil and Penny Knight Campus for Accelerating Scientific Impact University of Oregon Eugene OR 97403 USA

Translational Chemical Biology Group Division of Macromolecular Chemistry Department of Chemistry‐Ångström Laboratory Uppsala University Uppsala SE75121 Sweden

Cellular and Molecular Biotechnology Research Institute (CMB) National Institute of Advanced Industrial Science and Technology (AIST) AIST Tsukuba Central 5, 111 Higashi Tsukuba Ibaraki 3058565 Japan

Department of Immunology Genetics and Pathology (IGP) Uppsala University Dag Hammarskjölds väg 20 Uppsala 75185 Sweden

Department of Clinical Sciences Swedish University of Agricultural Sciences Uppsala 75105 Sweden

Translational Cancer Medicine Research Program Faculty of Medicine University of Helsinki Helsinki 00010 Finland

School of Pharmacy and Pharmaceutical Sciences Cardiff University King Edward VII Avenue Cardiff CF10 3NB UK

Funding

Academy of Finland · Suomen Kulttuurirahasto · Pirkanmaan Rahasto · Sigrid Juséliuksen Säätiö

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