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

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

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 nanocomp...

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Bibliographic Details
Main Authors: Yuting Zhao, Jiayu Yuan, Yao Qi, Mengdi Sun, Yifei Zhang, Ge Zhang, Xiangchen Su, Mingzhu Song, Ruizhen Lv, Yijie Shi, Liang Zhao
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Materials Today Bio
Subjects:
Glioblastoma
Imprinted nanocomposites
Transferrin
Cholesterol
Cuproptosis
Immunogenic cell death
Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425007793
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Summary: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 via specific binding with transferrin receptors (TfR) highly expressed on the surface of GL261 cells. After intracellular internalization, DOX@MINPs-TRF/ChO conferred lysosome escape via proton sponge effects and demonstrated GSH responsive intracellular release of DOX and Cu2+ with the participation of disulfide bonds. As a result, it not only potentiated the synergistic induction of cuproptosis/apoptosis but also enhanced immunogenic cell death (ICD) effect. Furthermore, DOX@MINPs-TRF/ChO downregulated both PD-1 and PD-L1 expression through the specifical adsorption of ChO, remodeling the ChO metabolism axis in tumor regions and maintaining the immune-checkpoint blockade (ICB) effect. Collectively, DOX@MINPs-TRF/ChO induced synergistic cuproptosis/ICB/ICD and represented a potent strategy for enhancing treatment in GL261 glioma-bearing mice.
ISSN:2590-0064

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