Modified-chitosan/siRNA nanoparticles downregulate cellular CDX2 expression and cross the gastric mucus barrier.
Development of effective non-viral vectors is of crucial importance in the implementation of RNA interference in clinical routine. The localized delivery of siRNAs to the gastrointestinal mucosa is highly desired but faces specific problems such as the stability in gastric acidity conditions and the...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4055692?pdf=render |
| _version_ | 1811307233832599552 |
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| author | Ana Sadio Jenny K Gustafsson Bruno Pereira Carla Pereira Gomes Gunnar C Hansson Leonor David Ana Paula Pêgo Raquel Almeida |
| author_facet | Ana Sadio Jenny K Gustafsson Bruno Pereira Carla Pereira Gomes Gunnar C Hansson Leonor David Ana Paula Pêgo Raquel Almeida |
| author_sort | Ana Sadio |
| collection | DOAJ |
| description | Development of effective non-viral vectors is of crucial importance in the implementation of RNA interference in clinical routine. The localized delivery of siRNAs to the gastrointestinal mucosa is highly desired but faces specific problems such as the stability in gastric acidity conditions and the presence of the mucus barrier. CDX2 is a transcription factor critical for intestinal differentiation being involved in the initiation and maintenance of gastrointestinal diseases. Specifically, it is the trigger of gastric intestinal metaplasia which is a precursor lesion of gastric cancer. Its expression is also altered in colorectal cancer, where it may constitute a lineage-survival oncogene. Our main objective was to develop a nanoparticle-delivery system of siRNA targeting CDX2 using modified chitosan as a vector. CDX2 expression was assessed in gastric carcinoma cell lines and nanoparticles behaviour in gastrointestinal mucus was tested in mouse explants. We show that imidazole-modified chitosan and trimethylchitosan/siRNA nanoparticles are able to downregulate CDX2 expression and overpass the gastric mucus layer but not colonic mucus. This system might constitute a potential therapeutic approach to treat CDX2-dependent gastric lesions. |
| first_indexed | 2024-04-13T09:00:37Z |
| format | Article |
| id | doaj.art-0adaf4caa75c41c7875290f6414e07d8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T09:00:37Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0adaf4caa75c41c7875290f6414e07d82022-12-22T02:53:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0196e9944910.1371/journal.pone.0099449Modified-chitosan/siRNA nanoparticles downregulate cellular CDX2 expression and cross the gastric mucus barrier.Ana SadioJenny K GustafssonBruno PereiraCarla Pereira GomesGunnar C HanssonLeonor DavidAna Paula PêgoRaquel AlmeidaDevelopment of effective non-viral vectors is of crucial importance in the implementation of RNA interference in clinical routine. The localized delivery of siRNAs to the gastrointestinal mucosa is highly desired but faces specific problems such as the stability in gastric acidity conditions and the presence of the mucus barrier. CDX2 is a transcription factor critical for intestinal differentiation being involved in the initiation and maintenance of gastrointestinal diseases. Specifically, it is the trigger of gastric intestinal metaplasia which is a precursor lesion of gastric cancer. Its expression is also altered in colorectal cancer, where it may constitute a lineage-survival oncogene. Our main objective was to develop a nanoparticle-delivery system of siRNA targeting CDX2 using modified chitosan as a vector. CDX2 expression was assessed in gastric carcinoma cell lines and nanoparticles behaviour in gastrointestinal mucus was tested in mouse explants. We show that imidazole-modified chitosan and trimethylchitosan/siRNA nanoparticles are able to downregulate CDX2 expression and overpass the gastric mucus layer but not colonic mucus. This system might constitute a potential therapeutic approach to treat CDX2-dependent gastric lesions.http://europepmc.org/articles/PMC4055692?pdf=render |
| spellingShingle | Ana Sadio Jenny K Gustafsson Bruno Pereira Carla Pereira Gomes Gunnar C Hansson Leonor David Ana Paula Pêgo Raquel Almeida Modified-chitosan/siRNA nanoparticles downregulate cellular CDX2 expression and cross the gastric mucus barrier. PLoS ONE |
| title | Modified-chitosan/siRNA nanoparticles downregulate cellular CDX2 expression and cross the gastric mucus barrier. |
| title_full | Modified-chitosan/siRNA nanoparticles downregulate cellular CDX2 expression and cross the gastric mucus barrier. |
| title_fullStr | Modified-chitosan/siRNA nanoparticles downregulate cellular CDX2 expression and cross the gastric mucus barrier. |
| title_full_unstemmed | Modified-chitosan/siRNA nanoparticles downregulate cellular CDX2 expression and cross the gastric mucus barrier. |
| title_short | Modified-chitosan/siRNA nanoparticles downregulate cellular CDX2 expression and cross the gastric mucus barrier. |
| title_sort | modified chitosan sirna nanoparticles downregulate cellular cdx2 expression and cross the gastric mucus barrier |
| url | http://europepmc.org/articles/PMC4055692?pdf=render |
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