ArticleMolecular pharmaceutics2011
Interaction of poly(ethylenimine)-DNA polyplexes with mitochondria: implications for a mechanism of cytotoxicity.
Article in Molecular pharmaceutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 94 citations in OpenAlex.
- The development of DNA delivery system based on ionic liquid and carboxylic acid modified polyethyleneimine.Drug delivery · 2026Article
- Stimulus-Responsive Polymeric Carriers for Gene Delivery: Balancing Endosomal Escape with Nucleic Acid Release.Pharmaceutical research · 2026Review
- Advances in Polyethyleneimine-Derived Nanoformulations.Small science · 2026Review
- Rewriting Tumor Entry Rules: Microfluidic Polyplexes and Tumor-Penetrating Strategies-A Literature Review.Pharmaceutics · 2026Review
- The Nanoparticle Delivery Gap in Immune Cell Engineering: From Uptake to Endosomal Escape.International journal of nanomedicine · 2026Review
- Mechanism of nanomaterial-induced lipid droplet formation inFrontiers in plant science · 2025Article
- Dihydroxyphenylalanine-conjugated high molecular weight polyethylenimine for targeted delivery of Plasmid.Scientific reports · 2024Article
- Polymeric Vehicles for Nucleic Acid Delivery: Enhancing the Therapeutic Efficacy and Cellular Uptake.Recent advances in drug delivery and formulation · 2024Review
- Carboxymethylated Gums and Derivatization: Strategies and Significance in Drug Delivery and Tissue Engineering.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Article
- Endosomal Escape of Bioactives Deployed via Nanocarriers: Insights Into the Design of Polymeric Micelles.Pharmaceutical research · 2022Review
- Polyethyleneimine-Based Lipopolyplexes as Carriers in Anticancer Gene Therapies.Materials (Basel, Switzerland) · 2021Review
- Cyclopropenium Nanoparticles and Gene Transfection in Cells.Pharmaceutics · 2020Article
- Nanoparticle delivery of a pH-sensitive prodrug of doxorubicin and a mitochondrial targeting VES-HScientific reports · 2020Article
- Polymer-mediated gene therapy: Recent advances and merging of delivery techniques.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2020Review
- Polymeric vehicles for nucleic acid delivery.Advanced drug delivery reviews · 2020Review
- DNA Vaccines-How Far From Clinical Use?International journal of molecular sciences · 2018Review
- Comparison of Gene Transfection and Cytotoxicity Mechanisms of Linear Poly(amidoamine) and Branched Poly(ethyleneimine) Polyplexes.Pharmaceutical research · 2018Article
- Polyplex Evolution: Understanding Biology, Optimizing Performance.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Review
- Dual-Function Polymeric HPMA Prodrugs for the Delivery of miRNA.Molecular pharmaceutics · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Poly(ethylenimine) (PEI) and PEI-based systems have been widely studied for use as nucleic acid delivery vehicles. However, many of these vehicles display high cytotoxicity, rendering them unfit for therapeutic use. By exploring the mechanisms that cause cytotoxicity, and through understanding structure-function relationships between polymers and intracellular interactions, nucleic acid delivery vehicles with precise intracellular properties can be tailored for specific function. Previous research has shown that PEI is able to depolarize mitochondria, but the exact mechanism as to how depolarization is induced remains elusive and therefore is the focus of the current study. Potential mechanisms for mitochondrial depolarization include direct mitochondrial membrane permeabilization by PEI or PEI polyplexes, activation of the mitochondrial permeability transition pore, and interference with mitochondrial membrane proton pumps, specifically Complex I of the electron transport chain and F(0)F(1)-ATPase. Herein, confocal microscopy and live cell imaging showed that PEI polyplexes do colocalize to some degree with mitochondria early in transfection, and the degree of colocalization increases over time. Cyclosporin a was used to prevent activation of the mitochondrial membrane permeability transition pore, and it was found that early in transfection cyclosporin a was unable to prevent the loss of mitochondrial membrane potential. Further studies done using rotenone and oligomycin to inhibit Complex I of the electron transport chain and F(0)F(1)-ATPase, respectively, indicate that both of these mitochondrial proton pumps are functioning during PEI transfection. Overall, we conclude that direct interaction between polyplexes and mitochondria may be the reason why mitochondrial function is impaired during PEI transfection.
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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.