ArticleMaterials today. Bio2026
Localized delivery of hyaluronic acid-doxorubicin from a surgical paste for post-operative glioblastoma treatment.
Article in Materials today. Bio, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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12 authors.
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Abstract
Glioblastoma stem cells (GSCs) and residual tumor cells - which resist conventional therapies, drive disease recurrence, and contribute to the formation of an immunosuppressive tumor-immune microenvironment (TIME) - represent a crucial barrier to the effective treatment of post-operative glioblastoma, the most aggressive and lethal primary brain tumor in adults. The cavity left after tumor resection represents a valuable opportunity to deliver therapeutics locally via the placement of conformable scaffolds for the immediate chemotherapeutic targeting of GSCs and residual glioblastoma cells. We hypothesized that Surgiflo™, a moldable, FDA-approved gelatin-based hemostatic paste, could serve as a dual-purpose platform that minimizes postoperative bleeding and functions as a conformable, local, and sustained drug-delivery system. We incorporated a pH-sensitive designed hyaluronic acid-doxorubicin polymer-drug conjugate (HA-DOX) into the Surgiflo™ matrix, exploiting HA's selective affinity for CD44 (highly expressed by both GBM and GSCs) and promoting the depletion of GBM and GSCs via immunogenic cell death (ICD)-inducing properties of DOX. In vitro studies of HA-DOX-containing paste confirmed enhanced HA-DOX uptake in GSC-enriched models, improved ICD induction in GBM cells, favorable biocompatibility, and sustained drug release. In vivo evaluations revealed that intracavitary implantation of the HA-DOX-containing paste significantly prolonged the median survival of treated mice compared to the untreated group (37 days vs 25 days, respectively) and modulated the glioblastoma-associated TIME, resulting in a 44% reduction in GSC levels and a significant increase in CD8
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