ArticleACS nano2013
Balancing cationic and hydrophobic content of PEGylated siRNA polyplexes enhances endosome escape, stability, blood circulation time, and bioactivity in vivo.
Article in ACS nano, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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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.
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Who cites it
109 citing papers in PubMed, 289 citations in OpenAlex.
- Systematic engineering of Layer-by-Layer anti-miR coated wound dressings with tunable release kinetics.Biomaterials advances · 2026Article
- Bioinspired, Guanidinium, and Indole Modified Poly(glycidyl ether)s as Highly Efficient Vectors for Polyplex-Mediated Gene Delivery.Macromolecular rapid communications · 2026Article
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- Nanomedicines targeting protease-activated receptor 2 in endosomes provide sustained analgesia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Self-Immolative Polyion Complexes.Macromolecular rapid communications · 2025Article
- Emerging polymeric nanocarriers for mRNA and protein therapeutics: design, challenges, and clinical outlook.Nanomedicine (London, England) · 2025Review
- Acid-cleavable poly(oxazoline) surfactants.Polymer chemistry · 2025Article
- Nebulization of RNA-Loaded Micelle-Embedded Polyplexes as a Potential Treatment of Idiopathic Pulmonary Fibrosis.ACS applied materials & interfaces · 2025Article
- Covalent Polymer-RNA Conjugates for Potent Activation of the RIG-I Pathway.Advanced healthcare materials · 2025Article
- Article
- Injectable hydrogel encapsulating siMMP13 with anti-ROS and anti-apoptotic functions for osteoarthritis treatment.Journal of nanobiotechnology · 2024Article
- Poly(β-aminoester) Physicochemical Properties Govern the Delivery of siRNA from Electrostatically Assembled Coatings.Biomacromolecules · 2024Article
- Progress of nanomaterials in the treatment of thrombus.Drug delivery and translational research · 2024Review
- mRNA Delivery: Challenges and Advances through Polymeric Soft Nanoparticles.International journal of molecular sciences · 2024Review
- Poly(2-oxazoline)/saRNA Polyplexes for Targeted and Nonviral Gene Delivery.Biomacromolecules · 2023Article
- Effect of Polyplex Size on Penetration into Tumor Spheroids.Molecular pharmaceutics · 2023Article
- Engineering endosomolytic nanocarriers of diverse morphologies using confined impingement jet mixing.Nanoscale · 2023Article
- Understanding How Cationic Polymers' Properties Inform Toxic or Immunogenic Responses via Parametric Analysis.Macromolecules · 2023Article
- NonviralACS nano · 2023Article
- Electrostatically assembled wound dressings deliver pro-angiogenic anti-miRs preferentially to endothelial cells.Biomaterials · 2023Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
A family of pH-responsive diblock polymers composed of poly[(ethylene glycol)-b-[(2-(dimethylamino)ethyl methacrylate)-co-(butyl methacrylate)], PEG-(DMAEMA-co-BMA), was reversible addition-fragmentation chain transfer (RAFT) synthesized with 0-75 mol % BMA in the second polymer block. The relative mole % of DMAEMA and BMA was varied in order to identify a polymer that can be used to formulate PEGylated, siRNA-loaded polyplex nanoparticles (NPs) with an optimized balance of cationic and hydrophobic content in the NP core based on siRNA packaging, cytocompatibility, blood circulation half-life, endosomal escape, and in vivo bioactivity. The polymer with 50:50 mol % of DMAEMA:BMA (polymer "50 B") in the RAFT-polymerized block efficiently condensed siRNA into 100 nm NPs that displayed pH-dependent membrane disruptive behavior finely tuned for endosomal escape. In vitro delivery of siRNA with polymer 50 B produced up to 94% protein-level knockdown of the model gene luciferase. The PEG corona of the NPs blocked nonspecific interactions with constituents of human whole blood, and the relative hydrophobicity of polymer 50 B increased NP stability in the presence of human serum or the polyanion heparin. When injected intravenously, 50 B NPs enhanced blood circulation half-life 3-fold relative to more standard PEG-DMAEMA (0 B) NPs (p < 0.05), due to improved stability and a reduced rate of renal clearance. The 50 B NPs enhanced siRNA biodistribution to the liver and other organs and significantly increased gene silencing in the liver, kidneys, and spleen relative to the benchmark polymer 0 B (p < 0.05). These collective findings validate the functional significance of tuning the balance of cationic and hydrophobic content of polyplex NPs utilized for systemic siRNA delivery in vivo.
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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.