ArticleACS nano2019
A Combination of Tri-Leucine and Angiopep-2 Drives a Polyanionic Polymalic Acid Nanodrug Platform Across the Blood-Brain Barrier.
Article in ACS nano, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 85 citations in OpenAlex.
- Extracellular Vesicle-Mediated Nucleolin Transfer in Glioblastoma: A Targetable Axis Driving Blood-Tumour Barrier Formation.Journal of extracellular vesicles · 2026Article
- A Brain-Targeted Organophosphorus Hydrolase Fusion Protein Mediated by Angiopep-2 Neutralizes Central Organophosphates and Alleviates Neurotoxicity.International journal of nanomedicine · 2026Article
- Bionanoconjugates in Neurodegeneration: Peptide-Nanoparticle Alliances for Next-Generation Therapies.Pharmaceutical research · 2025Review
- Rapid in situ microwave-assisted fabrication of ultrabright near-infrared probe for low-dose in vivo inflammatory imaging.Journal of nanobiotechnology · 2025Article
- Blood-brain barrier crossing biopolymer targeting c-Myc and anti-PD-1 activate primary brain lymphoma immunity: Artificial intelligence analysis.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Drug delivery pathways to the central nervous system via the brain glymphatic system circumventing the blood-brain barrier.Exploration (Beijing, China) · 2025Review
- Nano-Polymers as Cas9 Inhibitors.Polymers · 2025Article
- Inorganic and hybrid nanomaterials for NIR-II fluorescence imaging-guided therapy of Glioblastoma and perspectives.Theranostics · 2025Review
- Nanocarriers based therapy and diagnosis of brain diseases: cross the blood-brain barrier.Science and technology of advanced materials · 2025Review
- PEGylated lipids in lipid nanoparticle delivery dynamics and therapeutic innovation.Beilstein journal of nanotechnology · 2025Review
- Improving treatment for Parkinson's disease: Harnessing photothermal and phagocytosis-driven delivery of levodopa nanocarriers across the blood-brain barrier.Asian journal of pharmaceutical sciences · 2024Article
- Glioma-Derived Exosomes and Their Application as Drug Nanoparticles.International journal of molecular sciences · 2024Review
- Hub genes, a diagnostic model, and immune infiltration based on ferroptosis-linked genes in schizophrenia.IBRO neuroscience reports · 2024Article
- Nanoparticles crossing blood-brain barrier need specific design for normal, neurodegenerative or cancerous brain conditions.Nanomedicine (London, England) · 2024Article
- Targeted Boron Neutron Capture Therapy Using Polymalic Acid Derived Nano-Boron to Treat Glioblastoma.Journal of oncology research and therapy · 2024Article
- Novel Approaches to the Establishment of Local Microenvironment from Resorbable Biomaterials in the Brain In Vitro Models.International journal of molecular sciences · 2023Review
- Interactions of Nanoscale Self-Assembled Peptide-Based Assemblies with Glioblastoma Cell Models and Spheroids.ACS omega · 2023Article
- New Boron Delivery Agents.Cancer biotherapy & radiopharmaceuticals · 2023Review
- Nanoparticle Targeting with Antibodies in the Central Nervous System.BME frontiers · 2023Review
- Preserving and enhancing mitochondrial function after stroke to protect and repair the neurovascular unit: novel opportunities for nanoparticle-based drug delivery.Frontiers in cellular neuroscience · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
One of the major problems facing the treatment of neurological disorders is the poor delivery of therapeutic agents into the brain. Our goal is to develop a multifunctional and biodegradable nanodrug delivery system that crosses the blood-brain barrier (BBB) to access brain tissues affected by neurological disease. In this study, we synthesized a biodegradable nontoxic β-poly(l-malic acid) (PMLA or P) as a scaffold to chemically bind the BBB crossing peptides Angiopep-2 (AP2), MiniAp-4 (M4), and the transferrin receptor ligands cTfRL and B6. In addition, a trileucine endosome escape unit (LLL) and a fluorescent marker (rhodamine or rh) were attached to the PMLA backbone. The pharmacokinetics, BBB penetration, and biodistribution of nanoconjugates were studied in different brain regions and at multiple time points via optical imaging. The optimal nanoconjugate, P/LLL/AP2/rh, produced significant fluorescence in the parenchyma of cortical layers II/III, the midbrain colliculi, and the hippocampal CA1-3 cellular layers 30 min after a single intravenous injection; clearance was observed after 4 h. The nanoconjugate variant P/LLL/rh lacking AP2, or the variant P/AP2/rh lacking LLL, showed significantly less BBB penetration. The LLL moiety appeared to stabilize the nanoconjugate, while AP2 enhanced BBB penetration. Finally, nanoconjugates containing the peptides M4, cTfRL, and B6 displayed comparably little and/or inconsistent infiltration of brain parenchyma, likely due to reduced trans-BBB movement. P/LLL/AP2/rh can now be functionalized with intra-brain targeting and drug treatment moieties that are aimed at molecular pathways implicated in neurological disorders.
Indexed as
Identifiers
What OpenQuestion holds
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.