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The Proton Sponge: a Trick to Enter Cells the Viruses Did Not Exploit
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Several non-permanent polycations possessing substantial buffering capacity below physiological pH, such as lipopolyamines and polyethylenimines, are efficient transfection agents per se, i.e. without the addition of lysosomotropic bases, or cell targeting, or membrane disruption agents. These vectors have been shown to deliver genes as well as oligonucleotides both in vitro and in vivo. Our hypothesis is that their efficiency relies on extensive endosome swelling and rupture that provides an escape mechanism for the polycation/DNA particles.
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“Briefly, 2° and 3° amines on polymer chains can be protonated inside endo-lysosomes and then counterbalance chloride ions flow into the vesicles. This process creates an osmotic gradient between the exterior and interior of the endo-lysosomes, leading to swelling and bursting of these vesicles and releasing the polyplex into the cytosol [178].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [178]
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“…NPs and lipid-based NPs. Cationic NPs ( 3 , 4 ) escape endosomes via the “proton sponge effect”; the amine groups buffer endosomal pH, trigger endosomal accumulation of H + (and coun-terbalancing Cl − ), and contribute to an elevated osmotic pressure, membrane rupture, and cytosolic release ( 5 ).”
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“Hypo-thetically, protonation of the histidine residues induces an osmotic imbalance, leading to water in fl ux and endosomal swelling — a phenomenon known as the proton sponge effect 47 .”
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Metadata
- Authors
- Behr, J.-P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Behr, Jean-Paul
- Venue
- CHIMIA
- Publisher
- Swiss Chemical Society
- Published
- 1997-02-26
- Volume
- 51
- Issue
- 1-2
- Pages
- 34
- ISSN
- 0009-4293 (ISSN-L)
- 2673-2424
- OpenAlex
- W4292328694
- Cited by
- 933
- References
- 1
- Citations by year
- 2026: 18 · 2025: 31 · 2024: 30 · 2023: 34 · 2022: 24 · 2021: 41 · 2020: 56 · 2019: 47 · 2018: 50 · 2017: 38 · 2016: 58 · 2015: 50 · 2014: 55 · 2013: 78 · 2012: 49
- FWCI
- 1.07
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- CHIMIA International Journal for Chemistry (publishedVersion, cc-by-nc)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- proton sponge, polyethyleneimine, endosomal escape, gene delivery, oligonucleotide delivery, buffering capacity
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