ArticleJournal of controlled release : official journal of the Controlled Release Society2026
Single-ligand dual-targeting lipid nanoparticles for therapeutic mRNA delivery to glioblastoma across the blood-brain barrier.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
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Authors and funding
9 authors.
Funding
Abstract
Lipid nanoparticle (LNP)-mediated mRNA delivery to brain tumors is limited by the blood-brain barrier (BBB) and lack of active tumor targeting. Glucose transporter 1 (GLUT1), abundant on brain endothelium and overexpressed in glioblastoma, offers a single target for both BBB transcytosis and preferential tumor uptake. However, effective GLUT1 engagement requires high ligand densities on LNPs to compete with blood glucose, a threshold unattainable through conventional PEG-lipid functionalization. Furthermore, incorporating hydrophilic sugar ligands (e.g., glucose, mannose) can disrupt LNP architecture and mRNA encapsulation. Here, mannose-cholesterol LNPs (MC_LNPs) are developed to target GLUT1 and overcome these challenges. Mannose-cholesterol conjugation achieves ∼30 mol% surface ligand density, and incorporating positively charged DC-cholesterol restores >90% mRNA encapsulation. In healthy mice, MC_LNPs achieve 9.9-fold greater brain accumulation than non-targeted formulations, confirming BBB penetration. Functional delivery is validated using Cre mRNA in Ai14 reporter mice, revealing expression in neurons and astrocytes. In orthotopic glioblastoma models, phosphatase and tensin homolog (PTEN) mRNA-loaded MC_LNPs exhibit preferential tumor accumulation, restoring tumor suppression, reducing tumor burden 6-fold, and extending median survival from 33 to 49 days. MC-LNPs represent the first dual-targeted mRNA platform for brain tumors, establishing cholesterol-based functionalization as a strategy to achieve high ligand densities for efficient transporter/receptor targeting.
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Registered trials
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