ArticleBiomaterials2013
Distinct mechanisms of membrane permeation induced by two polymalic acid copolymers.
Article in Biomaterials, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 32 citations in OpenAlex.
- Unraveling Oral Fate of Poly(Lipoic Acid)s: Mechanistic Insights and Delivery Horizons.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Magnetic Resonance Imaging-Based Quantification of Endosomal Escape Using Iron Oxide Nanoparticle-Loaded Lipid Nanoparticles.Advanced healthcare materials · 2025Article
- Nano-Polymers as Cas9 Inhibitors.Polymers · 2025Article
- Article
- Polymalic acid for translational nanomedicine.Journal of nanobiotechnology · 2022Review
- Small-Sized Co-Polymers for Targeted Delivery of Multiple Imaging and Therapeutic Agents.Nanomaterials (Basel, Switzerland) · 2021Review
- Evaluation of the stability of a spray-dried tuberculosis vaccine candidate designed for dry powder respiratory delivery.Vaccine · 2021Article
- Biosynthetic Polymalic Acid as a Delivery Nanoplatform for Translational Cancer Medicine.Trends in biochemical sciences · 2021Review
- The Role of NK Cells and Innate Lymphoid Cells in Brain Cancer.Frontiers in immunology · 2020Review
- Blood-brain barrier permeable nano immunoconjugates induce local immune responses for glioma therapy.Nature communications · 2019Article
- Polymalic acid chlorotoxin nanoconjugate for near-infrared fluorescence guided resection of glioblastoma multiforme.Biomaterials · 2019Article
- A Combination of Tri-Leucine and Angiopep-2 Drives a Polyanionic Polymalic Acid Nanodrug Platform Across the Blood-Brain Barrier.ACS nano · 2019Article
- Covalent nano delivery systems for selective imaging and treatment of brain tumors.Advanced drug delivery reviews · 2017Review
- Polymalic Acid Tritryptophan Copolymer Interacts with Lipid Membrane Resulting in Membrane Solubilization.Journal of nanomaterials · 2017Article
- Quantitative analysis of PMLA nanoconjugate components after backbone cleavage.International journal of molecular sciences · 2015Article
- Macromolecular therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2014Review
- Toxicity and efficacy evaluation of multiple targeted polymalic acid conjugates for triple-negative breast cancer treatment.Journal of drug targeting · 2013Article
- Polymalic acid nanobioconjugate for simultaneous immunostimulation and inhibition of tumor growth in HER2/neu-positive breast cancer.Journal of controlled release : official journal of the Controlled Release Society · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Anionic polymers are valuable components used in cosmetics and health sciences, especially in drug delivery, because of their chemical versatility and low toxicity. However, because of their highly negative charge they pose problems for penetration through hydrophobic barriers such as membranes. We have engineered anionic polymalic acid (PMLA) to penetrate biological membranes. PMLA copolymers of leucine ethyl ester (P/LOEt) or trileucine (P/LLL) show either pH-independent or pH-dependent activity for membrane penetration. We report here for the first time on the mechanisms which are different for those two copolymers. Formation of hydrophobic patches in either copolymer is detected by fluorescence techniques. The copolymers display distinctly different properties in solution and during membranolysis. P/LOEt copolymer binds to membrane as single molecules with high affinity, and induces leakage cooperatively through a mechanism known as "carpet" model, in which the polymer aligns at the surface throughout the entire process of membrane permeation. In contrast, P/LLL self-assembles to form an oligomer of 105 nm in a pH-dependent manner (pKa 5.5) and induces membrane leakage through a two-phase process: the concentration dependent first-phase of insertion of the oligomer into membrane followed by a concentration independent second-phase of rearrangement of the membrane-oligomer complex. The insertion of P/LLL is facilitated by hydrophobic interactions between trileucine side chains and lipids in the membrane core, resulting in transmembrane pores, through mechanism known as "barrel-stave" model. The understanding of the mechanism paves the way for future engineering of polymeric delivery systems with optimal cytoplasmic delivery efficiency and reduced systemic toxicity.
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.