Dual molecularly imprinted nanocomposite with transferrin mediated glioma targeting and cholesterol exhaustion for synergistic cuproptosis/immune checkpoint blockade/immunogenic cell death. (2025)

Effective therapies for Glioblastoma (GBM) are often challenging by virtue of the intracranial location of GBM tumors, molecular heterogeneity, high recurrence rate, and overall resistance to treatment. Therefore, we proposed the development of doxorubicin (DOX) loaded molecularly imprinted nanocomposites (DOX@MINPs-TRF/ChO) using transferrin (TRF) and cholesterol (ChO) as dual-template and Cu nanoparticles (Cu@BSNs) as a functional monomer for enhancing the treatment of GBM. The results showed that DOX@MINPs-TRF/ChO specifically and effectively adsorbed TRF in blood circulation and subsequently enhanced the brain tumor targeting capability specific binding with transferrin receptors (TfR) highly expressed on the surface of GL261 cells. After intracellular internalization, DOX@MINPs-TRF/C