Postoperatively injected gel with sequential delivery of platinum agents to synergize with radiotherapy for suppressing high-grade glioma relapse
Journal
Chemical Engineering Journal
Journal Volume
522
Start Page
167569
ISSN
13858947
Date Issued
2025-10-15
Author(s)
Abstract
High-grade gliomas (HGGs) pose formidable clinical challenges given their poor prognosis and high recurrence rates. The current standard treatment of chemoradiotherapy involving systemic drug delivery of temozolomide with delayed radiotherapy is inadequate as it barely improves the median survival. The 3-week latency period between tumor resection and radiotherapy often causes infiltrative glioma regrowth within several months. A gel composite equipped with sequential delivery of platinum anticancer agents is presented here; the gel can be directly injected into the postresection cavity for prolonged release of anticancer agents to maintain topical effective drug concentration while synergizing with subsequent radiotherapy. The gel system comprises carboplatin to suppress the glioma growth initially and platinum-doped CaCO3 to subsequently deliver alkylating agents intracellularly via glioma cell endocytosis. The pH-dependent release of modified CaCO3 prolongs the release of the platinum agents. The gel system induces glioma cell apoptosis directly or can cause severe DNA lesions. Accordingly, reduced doses of radiotherapy can eliminate the infiltrating glioma tissue through synergistic effects. The postoperatively injected gel exhibits superior and prolonged antitumor effects with radiation in the orthotopic brain tumor model, further suppressing glioma relapse. Thus, the proposed drug-delivery system would be an ideal treatment combination for improving HGG prognosis.
Subjects
Calcium carbonate
Carboplatin
High-grade glioma
Radiotherapy
Sequential drug delivery
Synergistic effect
SDGs
Publisher
Elsevier B.V.
Type
journal article