ArticleMolecular pharmaceutics2012
Membrane and nuclear permeabilization by polymeric pDNA vehicles: efficient method for gene delivery or mechanism of cytotoxicity?
Article in Molecular pharmaceutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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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.
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.
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Who cites it
41 citing papers in PubMed, 107 citations in OpenAlex.
- Silica nanoparticles as advanced platforms for nucleic acid delivery.Materials today. Bio · 2026Review
- Chemical Constituents, Antioxidant Potential, and Antimicrobial Efficacy ofMicroorganisms · 2023Article
- Still finding ways to augment the existing management of acute and chronic kidney diseases with targeted gene and cell therapies: Opportunities and hurdles.Frontiers in medicine · 2023Review
- CNS Delivery of Nucleic Acid Therapeutics: Beyond the Blood-Brain Barrier and Towards Specific Cellular Targeting.Pharmaceutical research · 2023Review
- The Progress of Non-Viral Materials and Methods for Gene Delivery to Skeletal Muscle.Pharmaceutics · 2022Review
- Non-viral delivery of CRISPR-Cas9 complexes for targeted gene editing via a polymer delivery system.Gene therapy · 2022Article
- Review
- Targeting the Inside of Cells with Biologicals: Chemicals as a Delivery Strategy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Review
- Two Antibody-Guided Lactic-co-Glycolic Acid-Polyethylenimine (LGA-PEI) Nanoparticle Delivery Systems for Therapeutic Nucleic Acids.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Gene- and RNAi-activated scaffolds for bone tissue engineering: Current progress and future directions.Advanced drug delivery reviews · 2021Review
- Charge-Conversion Strategies for Nucleic Acid Delivery.Advanced functional materials · 2021Article
- Article
- Polymer-mediated gene therapy: Recent advances and merging of delivery techniques.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2020Review
- Engineered Polymeric Materials for Biological Applications: Overcoming Challenges of the Bio-Nano Interface.Polymers · 2019Review
- Synthetic Approaches for Nucleic Acid Delivery: Choosing the Right Carriers.Life (Basel, Switzerland) · 2019Review
- Dual carrier-cargo hydrophobization and charge ratio optimization improve the systemic circulation and safety of zwitterionic nano-polyplexes.Biomaterials · 2019Article
- Pharmacological profiling of sigma 1 receptor ligands by novel receptor homomer assays.Neuropharmacology · 2018Article
- Comparison of Gene Transfection and Cytotoxicity Mechanisms of Linear Poly(amidoamine) and Branched Poly(ethyleneimine) Polyplexes.Pharmaceutical research · 2018Article
- Non-viral Delivery of Nucleic Acids: Insight Into Mechanisms of Overcoming Intracellular Barriers.Frontiers in pharmacology · 2018Review
- Solid-phase supported design of carriers for therapeutic nucleic acid delivery.Bioscience reports · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The aim of this study is to compare the cytotoxicity mechanisms of linear PEI to two analogous polymers synthesized by our group: a hydroxyl-containing poly(l-tartaramidoamine) (T4) and a version containing an alkyl chain spacer poly(adipamidopentaethylenetetramine) (A4) by studying the cellular responses to polymer transfection. We have also synthesized analogues of T4 with different molecular weights (degrees of polymerization of 6, 12, and 43) to examine the role of molecular weight on the cytotoxicity mechanisms. Several mechanisms of polymer-induced cytotoxicity are investigated, including plasma membrane permeabilization, the formation of potentially harmful polymer degradation products during transfection including reactive oxygen species, and nuclear membrane permeabilization. We hypothesized that since cationic polymers are capable of disrupting the plasma membrane, they may also be capable of disrupting the nuclear envelope, which could be a potential mechanism of how the pDNA is delivered into the nucleus (other than nuclear envelope breakdown during mitosis). Using flow cytometry and confocal microscopy, we show that the polycations with the highest amount of protein expression and toxicity, PEI and T4(43), are capable of inducing nuclear membrane permeability. This finding is important for the field of nucleic acid delivery in that direct nucleus permeabilization could be not only a mechanism for pDNA nuclear import but also a potential mechanism of cytotoxicity and cell death. We also show that the production of reactive oxygen species is not a main mechanism of cytotoxicity, and that the presence or absence of hydroxyl groups and polymer length play a role in polyplex size and charge in addition to protein expression efficiency and toxicity.
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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.