ArticleJournal of nanobiotechnology2025
An anti-CD19-exosome delivery system navigates the blood-brain barrier for targeting of central nervous system lymphoma.
Article in Journal of nanobiotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Exosomes in brain diseases: Mechanisms, advances, and perspectives.Bioactive materials · 2027Review
- Extracellular vesicles in solid tumors: from tumor ecology to engineered therapeutics.Molecular cancer · 2026Review
- Engineered Exosomes in Precision Neuro-Oncology: Mechanisms, Therapeutics, and Translational Challenges.Cancers · 2026Review
- From LNPs to hybrid nanocarriers: development, challenges and redesign of non-viral gene delivery.Journal of nanobiotechnology · 2026Review
- Orchestrating organotropism: miRNA-driven mechanisms of site-specific metastasis in triple-negative breast cancer (Review).Oncology letters · 2026Review
- Mechanistic insights and therapeutic interventions of mitochondrial quality control in chemotherapy-related cognitive impairment.Neoplasia (New York, N.Y.) · 2026Review
- Enhancement of host anti-mycobacterial immunity by green tea hot-water extract is mediated through miR-9-5p-enriched lung extracellular vesicles.Frontiers in immunology · 2026Article
- Biomimetic PD-1-MSCs membrane-engineered nanoparticles for enhanced blood-brain barrier penetration and anti- glioma therapy.Frontiers in immunology · 2026Article
- Exosome Augmentation Technologies for Drug Delivery and Disease Treatment: A Review.Biomaterials research · 2026Review
- Extracellular vesicle therapeutics in Alzheimer's disease: mechanisms, progress, and prospects.Extracellular vesicles and circulating nucleic acids · 2026Review
- From Uptake to Therapeutic Function in Engineered Exosome Delivery Systems.Research (Washington, D.C.) · 2026Review
- Smart Cells Against Cancer: Advances in Cell-Based Drug Delivery and Diagnostics.Pharmaceutics · 2025Review
- Redefining the Limits of Nanodevices-Based Drug Delivery Systems: Extracellular Vesicles.Pharmaceutics · 2025Review
- Liposomal glytrexate formulation: improving antitumour efficacy and minimizing toxicity in breast cancer therapy.International journal of pharmaceutics: X · 2025Article
- Current Understanding of Protein Aggregation in Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Emerging Roles of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Therapy of Periodontitis.Biomedicines · 2025Review
- Unveiling the intricacies of exosome biology: from biogenesis to therapeutic applications.Histochemistry and cell biology · 2025Review
- Immunoelectron microscopy: a comprehensive guide from sample preparation to high-resolution imaging.Discover nano · 2025Review
- Cracking the Blood-Brain Barrier Code: Rational Nanomaterial Design for Next-Generation Neurological Therapies.Pharmaceutics · 2025Review
- Research progress on mRNA drug delivery strategies in the nervous system.Nanomedicine (London, England) · 2025Review
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Abstract
backgroundHigh-dose methotrexate (HD-MTX) serves as the cornerstone of central nervous system lymphoma (CNSL) treatment, but its efficacy is limited due to low blood-brain barrier (BBB) penetration and adverse effects. This study is focused on an exosome-based drug delivery approach aimed at enhancing BBB permeability, thereby reducing the required dosage of methotrexate (MTX) while ensuring specific targeting of CNSL.
methodsHuman adipose-derived mesenchymal stem cells (hAMSCs) were modified with a lentiviral vector encoding anti-CD19, incorporated into exosomes characterized by colloidal gold immunoelectron microscopy and Nano flow cytometry. MTX loaded into anti-CD19-Exos via co-incubation, assessed for loading and encapsulation efficiencies using HPLC. In vitro BBB model constructed using hCMEC/D3 and astrocytes to investigate BBB permeability. In vivo efficacy of anti-CD19-Exo-MTX evaluated in intracranial CNSL models using MRI. Biodistribution tracked with DiR-labeled exosomes, drug concentration in CSF measured by HPLC. LC-MS/MS identified and characterized exosomal proteins analyzed using GO Analysis. Neuroprotective effects of exosomal proteins assessed with TUNEL and Nissl staining on hippocampal neurons in CNSL models. Liver and kidney pathology, blood biochemical markers, and complete blood count evaluated exosomal protein effects on organ protection and MTX-induced myelosuppression.
resultsWe generated anti-CD19-Exo derived from hAMSCs. These adapted exosomes effectively encapsulated MTX, enhancing drug accessibility within lymphoma cells and sustained intracellular accumulation over an extended period. Notably, anti-CD19-Exo-MTX interacted with cerebrovascular endothelial cells and astrocytes of the BBB, leading to endocytosis and facilitating the transportation of MTX across the barrier. Anti-CD19-Exo-MTX outperformed free MTX in vitro, exhibiting a more potent lymphoma-suppressive effect (P < 0.05). In intracranial orthotopic CNSL models, anti-CD19-Exo-MTX exhibited a significantly reduced disease burden compared to both the MTX and Exo-MTX groups, along with prolonged overall survival (P < 0.05). CSF drug concentration analysis demonstrated enhanced stability and longer-lasting drug levels for anti-CD19-Exo-MTX. Anti-CD19-Exo-MTX exhibited precise CNSL targeting with no organ toxicity. Notably, our study highlighted the functional potential of reversal effect of hAMSCs-exosomes on MTX-induced neurotoxicity, hepatic and renal impairment, and myelosuppression.
conclusionsWe present anti-CD19-Exo-MTX as a promising exosome-based drug delivery platform that enhances BBB permeability and offers specific targeting for effective CNSL treatment with reduced adverse effects.
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