Phospholipid-modified glycogen nanoparticles for synergistic chemo-photothermal treatment of glioblastoma.

Glioblastoma multiforme (GBM) remains one of the most aggressive central nervous system malignancies, with therapeutic efficacy severely constrained by the blood-brain barrier (BBB), which limits drug delivery to the tumor site, and by the lack of tumor-specific targeting, leading to off-target effects and inadequate intratumoral accumulation. To address these interconnected challenges, we designed a dual-targeted biomimetic nanoplatform (GIM@Lip-Bio/FA) using glycogen as a biodegradable core for co-loading methotrexate (MTX) and IR780, followed by coating with a lipid layer sequentially modified with biotin and folic acid (FA) to enable active transport across the BBB and selective recognition by glioma cells. The resulting nanoparticles exhibited a uniform size, excellent stability, and significantly enhanced cellular uptake mediated by SMVT and folate receptor α (FRα). Notably, the nanoplatform demonstrated efficient BBB penetration and precise tumor accumulation in orthotopic GBM models. Upon near-infrared irradiation, synergistic chemo-photothermal therapy was achieved, leading to effective suppression of tumor growth, with a 76% reduction in tumor volume compared to the control group. This work presents a promising strategy for targeted GBM therapy.