Therapeutic Reprogramming of Glioblastoma Phenotypic States Using Multifunctional Heparin Nanoparticles.

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

SUBMITTER: Le Joncour V 

PROVIDER: S-EPMC12806396 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature