ArticleBritish journal of pharmacology2012
The association of statins plus LDL receptor-targeted liposome-encapsulated doxorubicin increases in vitro drug delivery across blood-brain barrier cells.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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
34 citing papers in PubMed, 79 citations in OpenAlex.
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- Thymine-Modified Nanocarrier for Doxorubicin Delivery in Glioblastoma Cells.Molecules (Basel, Switzerland) · 2023Article
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- Low-density lipoprotein nanomedicines: mechanisms of targeting, biology, and theranostic potential.Drug delivery · 2021Review
- Blood-Brain Barrier in Brain Tumors: Biology and Clinical Relevance.International journal of molecular sciences · 2021Review
- Optimizing the Design of Blood-Brain Barrier-Penetrating Polymer-Lipid-Hybrid Nanoparticles for Delivering Anticancer Drugs to Glioblastoma.Pharmaceutical research · 2021Article
- Evolution of blood-brain barrier in brain diseases and related systemic nanoscale brain-targeting drug delivery strategies.Acta pharmaceutica Sinica. B · 2021Review
- SPION and doxorubicin-loaded polymeric nanocarriers for glioblastoma theranostics.Drug delivery and translational research · 2021Article
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- Editorial: Targeting Lipid Rafts as a Strategy Against Infection and Cancer.Frontiers in cell and developmental biology · 2021Article
- New Insights Into Targeting Membrane Lipids for Cancer Therapy.Frontiers in cell and developmental biology · 2020Review
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Corrections and comments
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Authors and funding
8 authors at 5 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe passage of drugs across the blood-brain barrier (BBB) limits the efficacy of chemotherapy in brain tumours. For instance, the anticancer drug doxorubicin, which is effective against glioblastoma in vitro, has poor efficacy in vivo, because it is extruded by P-glycoprotein (Pgp/ABCB1), multidrug resistance-related proteins and breast cancer resistance protein (BCRP/ABCG2) in BBB cells. The aim of this study was to convert poorly permeant drugs like doxorubicin into drugs able to cross the BBB. EXPERIMENTAL APPROACH: Experiments were performed on primary human cerebral microvascular endothelial hCMEC/D3 cells, alone and co-cultured with human brain and epithelial tumour cells. KEY
resultsStatins reduced the efflux activity of Pgp/ABCB1 and BCRP/ABCG2 in hCMEC/D3 cells by increasing the synthesis of NO, which elicits the nitration of critical tyrosine residues on these transporters. Statins also increased the number of low-density lipoprotein (LDL) receptors exposed on the surface of BBB cells, as well as on tumour cells like human glioblastoma. We showed that the association of statins plus drug-loaded nanoparticles engineered as LDLs was effective as a vehicle for non-permeant drugs like doxorubicin to cross the BBB, allowing its delivery into primary and metastatic brain tumour cells and to achieve significant anti-tumour cytotoxicity. CONCLUSIONS AND IMPLICATIONS: We suggest that our 'Trojan horse' approach, based on the administration of statins plus a LDL receptor-targeted liposomal drug, might have potential applications in the pharmacological therapy of different brain diseases for which the BBB represents an obstacle.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.