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oai:figshare.com:article/34044504 2026-10-01T11:19:09Z category_1 category_4 category_146 category_12 category_13 category_14 category_19 category_21 category_873 category_734 category_64 portal_63 item_type_6 month_year_10_2026

DSPE-Based Ligand-Cross-Linked Lipid Nanoparticles for BBB/BBTB Transport and Glioma Targeting Menghuan Tang (25156254) Yanyu Huang (589921) Qiufang Zong (6724151) Ruohao Fan (9972851) Md Saiful I. Chowdhury (11569870) Nhung Thi Hong Au (25156257) Kelsey Jane Racacho (25156260) Athena Sabaten Aragon (25156263) Francisco Javier Castaneda (25156266) Adam Abdelkhaleq (25156269) Tzu-Yin Lin (1830322) Yuanpei Li (446340) Biophysics Biochemistry Space Science Cell Biology Genetics Molecular Biology Pharmacology Biotechnology Chemical Sciences not elsewhere classified Biological Sciences not elsewhere classified Cancer single nanoparticle platform magnetic resonance imaging linked lnp platform limited active targeting improve therapeutic delivery 3 -( propionamido orthotopic glioma model glioma cell surfaces effective glioma therapy linked lipid nanoparticles recognize sialic acid maintaining formulation tunability restricted transport across free vcr group combines sequential bbb )- functionalized dspe free vcr glioma treatments glioma cells integrate lipid defined lipid based lipid phenylboronic acid maltobionic acid formulation compatibility tumor volume tumor nanocarriers translational potential study establishes reproducible preparation prolonged survival primarily due microfluidic technology major obstacle loading flexibility loading capacity ligand conjugates interface engineering fold lower enabled controlled dblc lnps containing glycans brain tumor bbtb transport Insufficient drug accumulation at intracranial tumor sites remains a major obstacle to effective glioma therapy, primarily due to restricted transport across the blood–brain barrier (BBB)/blood–brain tumor barrier (BBTB) and limited active targeting to glioma cells. Here, we report DSPE-based ligand-cross-linked lipid nanoparticles (DBLC LNPs) that integrate lipid-interface engineering, ligand cross-linking, and sequential glioma targeting within a single nanoparticle platform. In this design, maltobionic acid (MA)-functionalized DSPE was incorporated to promote glucose transporter 1 (GLUT1)-mediated BBB/BBTB transport, while 3-(propionamido)phenylboronic acid (PAPBA)-functionalized DSPE was introduced to recognize sialic acid-containing glycans on glioma cell surfaces. Compared with many complex multifunctional brain-tumor nanocarriers, this DSPE-based lipid-interface design introduces transport and recognition through defined lipid-ligand conjugates, thereby reducing synthetic complexity while maintaining formulation tunability and cargo-loading flexibility. Microfluidic technology further enabled controlled and reproducible preparation of DBLC LNPs, supporting their formulation compatibility and translational potential. In an orthotopic glioma model, vincristine (VCR)-loaded DBLC LNPs significantly suppressed glioma growth and prolonged survival. Magnetic resonance imaging (MRI)-based 3D reconstruction analysis of brain tumor further showed that DBLC LNPs@VCR inhibited tumor growth more effectively than free VCR, with tumor volume more than 6-fold lower than that in the free VCR group. Together, this study establishes a DSPE-based ligand-cross-linked LNP platform that combines sequential BBB/BBTB transport, drug-loading capacity, and formulation compatibility to improve therapeutic delivery for glioma treatments. 2026-10-01T00:00:00Z Text Journal contribution 10.1021/acsnanomed.6c00185.s001 https://figshare.com/articles/journal_contribution/DSPE-Based_Ligand-Cross-Linked_Lipid_Nanoparticles_for_BBB_BBTB_Transport_and_Glioma_Targeting/34044504 CC BY-NC 4.0