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Open AccessJournal ArticleDOI

The Possible “Proton Sponge ” Effect of Polyethylenimine (PEI) Does Not Include Change in Lysosomal pH

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TLDR
Measurements of lysosomal pH as a function of PEI content and correlate the results to the "proton sponge " hypothesis show that PEI does not induce change in lysoomic pH as previously suggested and quantification ofPEI concentrations inLysosomes makes it uncertain that the " proton sponge ' effect is the dominant mechanism of polyplex escape.
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This article is published in Molecular Therapy.The article was published on 2013-01-01 and is currently open access. It has received 616 citations till now. The article focuses on the topics: Polyethylenimine.

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Citations
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Using macropinocytosis for intracellular delivery of therapeutic nucleic acids to tumour cells.

TL;DR: This article reviews the delivery systems reported to be taken up by macropinocytosis and identifies new opportunities for exploiting this pathway for the intracellular delivery of nucleic acids to tumour cells.
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Serum-resistant, reactive oxygen species (ROS)-potentiated gene delivery in cancer cells mediated by fluorinated, diselenide-crosslinked polyplexes.

TL;DR: DSe-PEI-F showed high transfection efficiencies in cancer cells in the presence of serum, outperforming the commercial reagent PEI 25k by several orders of magnitude.
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Double domain polyethylenimine-based nanoparticles for integrin receptor mediated delivery of plasmid DNA.

TL;DR: The results demonstrated the ability of the PEI conjugate in the formation of nanoparticles with the size of around 210 nm with higher buffering capacity and in vivo imaging of the polyplexes revealed that 99mTc-labeled PEI/plasmid DNA complexes accumulated in kidney and bladder 4 h post injection, suggesting this PEI derivative could be considered as an efficient targeted delivery system for plasmidDNA.
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Extracellular dsRNA: its function and mechanism of cellular uptake.

TL;DR: This review presents an overview of double-stranded RNA, addressing its roles in infection, autoimmunity, and host sensing mechanisms, with a focus on extracellular recognition and uptake by the cell.
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Enhancing dendritic cell activation and HIV vaccine effectiveness through nanoparticle vaccination.

TL;DR: Important advances in how ‘nanovaccinology’ can be used to develop safe and effective vaccines for HIV are summarized and the central role of dendritic cells in the immune response to vaccination is highlighted.
References
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Journal ArticleDOI

A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine

TL;DR: Together, these properties make PEI a promising vector for gene therapy and an outstanding core for the design of more sophisticated devices because its efficiency relies on extensive lysosome buffering that protects DNA from nuclease degradation, and consequent lysOSomal swelling and rupture that provide an escape mechanism for the PEI/DNA particles.
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Understanding biophysicochemical interactions at the nano–bio interface

TL;DR: Probing the various interfaces of nanoparticle/biological interfaces allows the development of predictive relationships between structure and activity that are determined by nanomaterial properties such as size, shape, surface chemistry, roughness and surface coatings.
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Nonviral Vectors for Gene Delivery

TL;DR: Two nonviral gene delivery systems using either biodegradable poly(D,Llactide-co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells.
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Exploring polyethylenimine-mediated DNA transfection and the proton sponge hypothesis.

TL;DR: The relatively high transfection efficiency of polyethylenimine vectors has been hypothesized to be due to their ability to avoid trafficking to degradative lysosomes, and according to the proton sponge hypothesis, the buffering capacity of PEI leads to osmotic swelling and rupture of endosome, resulting in the release of the vector into the cytoplasm.
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Chloride Accumulation and Swelling in Endosomes Enhances DNA Transfer by Polyamine-DNA Polyplexes

TL;DR: The results provide direct support for the proton sponge hypothesis and thus a rational basis for the design of improved non-viral vectors for gene delivery.
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