Self-assembling polypeptide-drug conjugates as innovative therapeutic candidates for glioblastoma treatment by enhancing intracranial residence time.

ABSTRACT:

Background

Glioblastoma (GBM) is the most lethal and incurable brain tumor, with limited treatment options. Systemic delivery of many promising drugs has proven inefficacious due to insufficient brain penetrance. Convection-enhanced delivery (CED) enables direct intracranial infusion of high drug concentrations. However, CED is impaired by rapid drug clearance from the brain, which diminishes its therapeutic benefits.

Methods

To develop CED-injectable therapeutics for GBM treatment, two polypeptides, XM147 and XM161, were engineered through tandem recombination of IL4Rα- or IL13Rα2-specific ligands with thermally responsive motifs. XM147-AZDye647 was created by labeling XM147 with the fluorescent dye AZDye647 to study clearance kinetics. Polypeptide-drug conjugates (PDCs), X

SUBMITTER: Gwon Y 

PROVIDER: S-EPMC12449142 | biostudies-literature | 2025 Jan-Dec

REPOSITORIES: biostudies-literature