ArticleInternational journal of nanomedicine2018
Mechanisms of the effectiveness of poly(ε-caprolactone) lipid-core nanocapsules loaded with methotrexate on glioblastoma multiforme treatment.
Article in International journal of nanomedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 28 citations in OpenAlex.
- Innovative Strategies of Nanocapsules for Maximizing Efficacy in Tumor Immunotherapy.International journal of nanomedicine · 2026Review
- Folic Acid-Decorated Lipidic Nanocapsules Co-Loaded with Atorvastatin and Curcumin to Enhance Glioma Targeting in Mice.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Breaking barriers: exploring blood-brain barrier crossing mechanisms with nanomedicine for effective glioma treatment.3 Biotech · 2025Review
- Construction of m6A-Related lncRNA Prognostic Signature Model and Immunomodulatory Effect in Glioblastoma Multiforme.Frontiers in oncology · 2022Article
- Antioxidant vitamins promote anticancer effects on low-concentration methotrexate-treated glioblastoma cells via enhancing the caspase-3 death pathway.Food science & nutrition · 2021Article
- Drug Delivery Nanosystems in Glioblastoma Multiforme Treatment: Current State of the Art.Current neuropharmacology · 2021Review
- Biomedical Applications of Multifunctional Polymeric Nanocarriers: A Review of Current Literature.International journal of nanomedicine · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe low penetration of drugs across the blood-brain barrier (BBB) compromises the delivery of chemotherapeutic agents to the brain parenchyma and contributes to the poor prognosis of glioblastoma multiforme (GBM). We investigated the efficacy of methotrexate-loaded lipid-core nanocapsules (MTX-LNC) administered by the oral route to treat murine GBM, its ability to cross the BBB, and the mechanisms of MTX-LNC uptake by cultured GL261 glioma and BV2 microglia cells. MATERIALS AND
methodsFemale C57B/6 mice were used in intravital microscopy assays to investigate the penetrance of rhodamine B-label MTX-LNC (RhoB/MTX-LNC) in the brain after oral or IV administration, and to evaluate the BBB integrity. Intracranial implantation of GL261 cells was undertaken to induce a murine GBM model, and the effectiveness of oral MTX or MTX-LNC treatments (started on Day 10 of GBM, every 2 days for 12 days) was quantified by tumor size, body weight, and leukogram. Pharmacological blockade of endocytic pathways was done to investigate the mechanisms of MTX-LNC uptake by cultured GL261 and microglia BV2 cells by using fluorescence microscopy. The effect of MTX-LNC or MTX on GL261 and BV2 proliferation was evaluated to compare the cytotoxicity of such compounds.
resultsRhoB/MTX-LNC was detected in brain parenchyma of mice after IV or oral administration, without any damage on BBB. Oral treatment with MTX-LNC reduced tumor volume and prevented weight loss and leukopenia in comparison to MTX-treated mice. MTX-LNC uptake by GL261 is caveolae-dependent, whereas endocytosis of MTX-LNC by BV2 occurs via phagocytosis and macropinocytosis. Both MTX-LNC and MTX reduced GL261 and BV2 proliferation; however, MTX-LNC showed higher efficacy in the inhibition of glioma proliferation.
conclusionTogether, we infer that the higher ability of MTX-LNC to cross the BBB and be captured by cancer and immune brain cells by different mechanisms is responsible for the higher efficacy of oral MTX-LNC treatment in GBM.
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