ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
The possible "proton sponge " effect of polyethylenimine (PEI) does not include change in lysosomal pH.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers.
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Who cites it
237 citing papers in PubMed, 706 citations in OpenAlex.
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- Stimulus-Responsive Polymeric Carriers for Gene Delivery: Balancing Endosomal Escape with Nucleic Acid Release.Pharmaceutical research · 2026Review
- Finding the sweet spot between complexation and cytosolic release with different molecular weight branched polyethyleneimine polymers for mRNA delivery.Drug delivery and translational research · 2026Article
- Recent advances in stimuli-responsive nanomaterials for the treatment of acute kidney injury.Journal of nanobiotechnology · 2026Review
- Multi-modal therapeutic approaches to inflammatory bowel disease: plant-derived compounds, nanoparticle drug delivery systems, and gene-based interventions.Molecular biology reports · 2026Review
- Endoplasmic reticulum stress induced autophagy alters cellular processing of cationic lipid delivered siRNAs.Drug delivery and translational research · 2026Article
- The Role of CRISPR and Its Therapeutic Applications in Glioblastoma.International journal of molecular sciences · 2026Review
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- Unraveling the structure-activity relationship of alloying in nanozyme design for synergistic tumor metabolic-immunotherapy.Journal of nanobiotechnology · 2026Article
- Toward Safe and Effective Gene Therapy: Non-Viral Nanostructured Delivery Systems.International journal of nanomedicine · 2026Review
- Nanoscale biointerfaces in inter-organelle communication: membrane contact sites, organelle trafficking, and cell fate control.Frontiers in cell and developmental biology · 2026Review
- The Nanoparticle Delivery Gap in Immune Cell Engineering: From Uptake to Endosomal Escape.International journal of nanomedicine · 2026Review
- Understanding of endo/lysosomal escape of nanomaterials in biomedical application.Smart molecules : open access · 2025Review
- Nanoparticles and Nanocarriers for Managing Plant Viral Diseases.Plants (Basel, Switzerland) · 2025Review
- Types of Bone Substitutes and Their Application in Regenerative Medicine: A Systematic Review.Journal of functional biomaterials · 2025Review
- Cyclodextrin-Based Delivery Systems for Flavonoids: Mechanisms, Advances, Formulation, and Application Opportunities.Antioxidants (Basel, Switzerland) · 2025Review
177 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polycations such as polyethylenimine (PEI) are used in many novel nonviral vector designs and there are continuous efforts to increase our mechanistic understanding of their interactions with cells. Even so, the mechanism of polyplex escape from the endosomal/lysosomal pathway after internalization is still elusive. The "proton sponge " hypothesis remains the most generally accepted mechanism, although it is heavily debated. This hypothesis is associated with the large buffering capacity of PEI and other polycations, which has been interpreted to cause an increase in lysosomal pH even though no conclusive proof has been provided. In the present study, we have used a nanoparticle pH sensor that was developed for pH measurements in the endosomal/lysosomal pathway. We have carried out quantitative measurements of lysosomal pH as a function of PEI content and correlate the results to the "proton sponge " hypothesis. Our measurements show that PEI does not induce change in lysosomal pH as previously suggested and quantification of PEI concentrations in lysosomes makes it uncertain that the "proton sponge " effect is the dominant mechanism of polyplex escape.
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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.