Endosomal size and membrane leakiness influence proton sponge-based rupture of endosomal vesicles
| Autor: | Jo Demeester, Peter Dubruel, Stefaan C. De Smedt, Katrien Remaut, Kevin Braeckmans, Lotte Vermeulen, Sangram Keshari Samal, Toon Brans |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
NUCLEIC-ACID DELIVERY Endosome ENDOCYTOSIS MEDIATED GENE DELIVERY General Physics and Astronomy CELLULAR UPTAKE DNA COMPLEXES 02 engineering and technology Endosomes endosomal escape Endocytosis Transfection ESCAPE Models Biological Permeability Cell Line 03 medical and health sciences Osmotic pressure Humans Polyethyleneimine General Materials Science proton sponge effect INTRACELLULAR DELIVERY A549 cell SYNTHETIC PHOSPHOLIPID-VESICLES HELA-CELLS biology Chemistry Vesicle General Engineering Biology and Life Sciences LINEAR POLYETHYLENIMINE DNA Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology biology.organism_classification gene therapy nanomedicine polyethylenimine Sponge 030104 developmental biology Membrane Biophysics Protons 0210 nano-technology HeLa Cells Plasmids |
| Zdroj: | ACS NANO |
| ISSN: | 1936-0851 1936-086X |
| Popis: | In gene therapy, endosomal escape represents a major bottleneck since nanoparticles often remain entrapped inside endosomes and are trafficked toward the lysosomes for degradation. A detailed understanding of the endosomal barrier would be beneficial for developing rational strategies to improve transfection and endosomal escape. By visualizing individual endosomal escape events in live cells, we obtain insight into mechanistic factors that influence proton sponge-based endosomal escape. In a comparative study, we found that HeLa cells treated with JetPEI/pDNA polyplexes have a 3.5-fold increased endosomal escape frequency compared to ARPE-19 cells. We found that endosomal size has a major impact on the escape capacity. The smaller HeLa endosomes are more easily ruptured by the proton sponge effect than the larger ARPE-19 endosomes, a finding supported by a mathematical model based on the underlying physical principles. Still, it remains intriguing that even in the small HeLa endosomes |
| Databáze: | OpenAIRE |
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