ArticleInternational journal of nanomedicine2015
Investigation of enzyme-sensitive lipid nanoparticles for delivery of siRNA to blood-brain barrier and glioma cells.
Article in International journal of nanomedicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 79 citations in OpenAlex.
- Pyroptosis as a novel therapeutic target in glioblastoma multiforme: Mechanisms, molecular insights, and therapeutic potential.Molecular therapy. Nucleic acids · 2026Review
- Long non-coding RNAs in glioblastoma: from molecular drivers to therapeutic targets.Frontiers in immunology · 2026Review
- Review
- Emerging lipid nanoparticle systems capable of efficient intramuscular RNA delivery.Nanomedicine (London, England) · 2025Review
- Clinical applications of oligonucleotides for cancer therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Targeted miRNA Delivery in Epilepsy: Mechanisms, Advances, and Therapeutic Potential.Molecular biology reports · 2025Review
- Targeting Brain Drug Delivery with Macromolecules Through Receptor-Mediated Transcytosis.Pharmaceutics · 2025Review
- Navigating the intricate in-vivo journey of lipid nanoparticles tailored for the targeted delivery of RNA therapeutics: a quality-by-design approach.Journal of nanobiotechnology · 2024Review
- Review
- Review
- ApoE-functionalization of nanoparticles for targeted brain delivery-a feasible method for polyplexes?Drug delivery and translational research · 2024Article
- Surface Functionalized Lipid Nanoparticles in Promoting Therapeutic Outcomes: An Insight View of the Dynamic Drug Delivery System.Current drug targets · 2024Review
- Non-Coding RNAs in Human Cancer and Other Diseases: Overview of the Diagnostic Potential.International journal of molecular sciences · 2023Review
- Directing the Way-Receptor and Chemical Targeting Strategies for Nucleic Acid Delivery.Pharmaceutical research · 2023Review
- Drug Delivery Systems with a "Tumor-Triggered" Targeting or Intracellular Drug Release Property Based on DePEGylation.Materials (Basel, Switzerland) · 2022Review
- Predictive high-throughput screening of PEGylated lipids in oligonucleotide-loaded lipid nanoparticles for neuronal gene silencing.Nanoscale advances · 2022Article
- Gather wisdom to overcome barriers: Well-designed nano-drug delivery systems for treating gliomas.Acta pharmaceutica Sinica. B · 2022Review
- Next-Generation Anti-Angiogenic Therapies as a Future Prospect for Glioma Immunotherapy; From Bench to Bedside.Frontiers in immunology · 2022Review
- Biological implications and clinical potential of invasion and migration related miRNAs in glioma.Frontiers in integrative neuroscience · 2022Review
- Lipid-based nanoparticles and RNA as innovative neuro-therapeutics.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clinical applications of siRNA for treating disorders in the central nervous system require development of systemic stable, safe, and effective delivery vehicles that are able to cross the impermeable blood-brain barrier (BBB). Engineering nanocarriers with low cellular interaction during systemic circulation, but with high uptake in targeted cells, is a great challenge and is further complicated by the BBB. As a first step in obtaining such a delivery system, this study aims at designing a lipid nanoparticle (LNP) able to efficiently encapsulate siRNA by a combination of titratable cationic lipids. The targeted delivery is obtained through the design of a two-stage system where the first step is conjugation of angiopep to the surface of the LNP for targeting the low-density lipoprotein receptor-related protein-1 expressed on the BBB. Second, the positively charged LNPs are masked with a negatively charged PEGylated (poly(ethylene glycol)) cleavable lipopeptide, which contains a recognition sequence for matrix metalloproteinases (MMPs), a class of enzymes often expressed in the tumor microenvironment and inflammatory BBB conditions. Proteolytic cleavage induces PEG release, including the release of four glutamic acid residues, providing a charge switch that triggers a shift of the LNP charge from weakly negative to positive, thus favoring cellular endocytosis and release of siRNA for high silencing efficiency. This work describes the development of this two-stage nanocarrier-system and evaluates the performance in brain endothelial and glioblastoma cells with respect to uptake and gene silencing efficiency. The ability of activation by MMP-triggered dePEGylation and charge shift is demonstrated to substantially increase the uptake and the silencing efficiency of the LNPs.
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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.