ArticleProceedings of the National Academy of Sciences of the United States of America2018
Mechanism of drug extrusion by brain endothelial cells via lysosomal drug trapping and disposal by neutrophils.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. 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.
- Vat Polymerization 3D Printing of Hydrogels With Tunable Porosity.Small methods · 2026Article
- Effect of high altitude on the pharmacokinetics and pharmacodynamics of valproate in epileptic rats.Frontiers in pharmacology · 2026Article
- A surrogate barrier model for high-throughput blood-brain barrier permeability prediction: integrating LLC-PK1-MOCK/MDR1 Cells and lysosomal trapping correction.Drug delivery · 2025Article
- Drug-drug interactions in targeted cancer therapies: a focus on tyrosine kinase inhibitors.Expert review of clinical pharmacology · 2025Review
- The blood-brain barrier: a help and a hindrance.Brain : a journal of neurology · 2025Review
- Nanotechnology Driven Lipid and Metalloid Based Formulations Targeting Blood-Brain Barrier (3B) for Brain Tumor.Indian journal of microbiology · 2025Article
- Plant-Based Products Originating from Serbia That Affect P-glycoprotein Activity.Molecules (Basel, Switzerland) · 2024Review
- Distinct uptake and elimination profiles for trastuzumab, human IgG, and biocytin-TMR in experimental HER2+ brain metastases of breast cancer.Neuro-oncology · 2024Article
- Impact of Obesity and Lysosomal Dysfunction on Chemoresistance in Ovarian Cancer.Biomedicines · 2024Review
- Review
- Temozolomide and flavonoids against glioma: from absorption and metabolism to exosomal delivery.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Targeting Lysosomes: A Strategy Against Chemoresistance in Cancer.Mini reviews in medicinal chemistry · 2024Review
- Targeting brain tumors with innovative nanocarriers: bridging the gap through the blood-brain barrier.Oncology research · 2024Review
- Lysosomes as a Target of Anticancer Therapy.International journal of molecular sciences · 2023Review
- The Impact of P-Glycoprotein on Opioid Analgesics: What's the Real Meaning in Pain Management and Palliative Care?International journal of molecular sciences · 2022Review
- Discerning the Role of Blood Brain Barrier Dysfunction in Alzheimer's Disease.Aging and disease · 2022Article
- P-glycoprotein: new insights into structure, physiological function, regulation and alterations in disease.Heliyon · 2022Review
- Temozolomide Efficacy and Metabolism: The Implicit Relevance of Nanoscale Delivery Systems.Molecules (Basel, Switzerland) · 2022Review
- Article
- Crossing the Blood-Brain Barrier: Advances in Nanoparticle Technology for Drug Delivery in Neuro-Oncology.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The blood-brain barrier protects the brain against a variety of potentially toxic compounds. Barrier function results from tight junctions between brain capillary endothelial cells and high expression of active efflux transporters, including P-glycoprotein (Pgp), at the apical membrane of these cells. In addition to actively transporting drugs out of the cell, Pgp mediates lysosomal sequestration of chemotherapeutic drugs in cancer cells, thus contributing to drug resistance. Here, we describe that lysosomal sequestration of Pgp substrates, including doxorubicin, also occurs in human and porcine brain endothelial cells that form the blood-brain barrier. This is followed by shedding of drug-sequestering vesicular structures, which stay attached to the apical side of the plasma membrane and form aggregates ("barrier bodies") that ultimately undergo phagocytosis by neutrophils, thus constituting an as-yet-undescribed mechanism of drug disposal. These findings introduce a mechanism that might contribute to brain protection against potentially toxic xenobiotics, including therapeutically important chemotherapeutic drugs.
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