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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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Journal ArticleDOI

Super-resolution Imaging of Proton Sponge-Triggered Rupture of Endosomes and Cytosolic Release of Small Interfering RNA.

TL;DR: It is found that the architecture of the polyplex and the rigidity of the cationic polymer chains are crucial parameters that control the mechanism of endosomal escape driven by the proton sponge effect.
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Leveraging Physiology for Precision Drug Delivery

TL;DR: A large number of drug delivery platforms have been devised ranging from macro- to micro-based systems, but how these are implemented and how they are implemented are still in the early stages.
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Fine-tuning of proton sponges by precise diaminoethanes and histidines in pDNA polyplexes.

TL;DR: In this article, the authors characterized the buffer capacity of proton-sponge transfection agents for pDNA delivery and demonstrated over 100fold enhanced transection and better endosomal escape by using receptor targeted and polyethylene glycol shielded polyplexes.
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Multifunctional polyamidoamine-modified selenium nanoparticles dual-delivering siRNA and cisplatin to A549/DDP cells for reversal multidrug resistance.

TL;DR: Animal studies demonstrated that the new delivery system of G5@Se-DDP-siRNA significantly enhanced the anti-tumor effect on tumor-bearing nude mice, with no appreciable abnormality in the major organs.
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Chitosan for gene delivery: Methods for improvement and applications.

TL;DR: The features of chitosan in gene delivery are introduced, current progress toward methods promoting the properties of ch itosan related to gene delivery is summarized, and different applications of chITosanIn gene delivery vectors are presented.
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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