GSCs differentiation model-informed nanotherapy: dual-functional brain-targeting liposomes with iRGD modification for co-delivery of osimertinib and bortezomib to combat radioresistant glioblastoma.

ABSTRACT: Radiation resistance in glioblastoma (GBM) poses a persistent clinical hurdle, driven in part by hyperactivated EGFR and NF-κB signaling. To recapitulate post-radiation tumor recurrence, we engineered radioresistant glioblastoma stem cells (GSCs) from U87-derived GSCs via 13 cycles of 5Gy irradiation (IR), yielding differentiated radioresistant progeny cells (Diff) that mimic the aggressive phenotype of recurrent GBM. Integrative analysis of RNA sequencing data from parental U87 cells, GSCs, and Diff cells-along with the TCGA database-identified coordinated EGFR and NF-κB (RelA/p65) signaling as central mediators of therapeutic resistance. Leveraging this insight, we designed iRGD-modified liposomes (iRGD-OB-LP) for targeted co-delivery of Osimertinib (EGFR inhibitor) and Bortezomib (NF-κB

SUBMITTER: Xie C 

PROVIDER: S-EPMC12540775 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature