biostudies-literatureUnknown7(1)Gwon Y<h4>Background</h4>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.<h4>Methods</h4>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), XNeuro-oncology advancesvdaf187https://www.ebi.ac.uk/biostudies/studies/S-EPMC12449142biostudies-literatureSelf-assembling polypeptide-drug conjugates as innovative therapeutic candidates for glioblastoma treatment by enhancing intracranial residence time.PMC12449142Kim SGwon YJung WJeon WBShin KKim JEChoi YCheon GJLee YfalseSelf-assembling polypeptide-drug conjugates as innovative therapeutic candidates for glioblastoma treatment by enhancing intracranial residence time.<h4>Background</h4>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.<h4>Methods</h4>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), X2025-01-01T00:00:00Z2025 Jan-Dec2026-06-03T16:59:57.796Z2026-04-29T03:13:05.978ZS-EPMC124491424098045010.1093/noajnl/vdaf187