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Study the lipidoid nanoparticle mediated genome editing protein delivery using 3D intestinal tissue model

Lipid nanoparticles are promising carriers for oral drug delivery. For bioactive cargos with intracellular targets, e.g. gene-editing proteins, it is essential for the cargo and carrier to remain complexed after crossing the epithelial layer of intestine in order for the delivery system to transport...

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Detalles Bibliográficos
Autores principales: Yang, Tao, Han, Haobo, Chen, Ying, Yang, Liu, Parker, Rachael, Li, Yamin, Kaplan, David L., Xu, Qiaobing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056182/
https://www.ncbi.nlm.nih.gov/pubmed/33898871
http://dx.doi.org/10.1016/j.bioactmat.2021.03.027
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author Yang, Tao
Han, Haobo
Chen, Ying
Yang, Liu
Parker, Rachael
Li, Yamin
Kaplan, David L.
Xu, Qiaobing
author_facet Yang, Tao
Han, Haobo
Chen, Ying
Yang, Liu
Parker, Rachael
Li, Yamin
Kaplan, David L.
Xu, Qiaobing
author_sort Yang, Tao
collection PubMed
description Lipid nanoparticles are promising carriers for oral drug delivery. For bioactive cargos with intracellular targets, e.g. gene-editing proteins, it is essential for the cargo and carrier to remain complexed after crossing the epithelial layer of intestine in order for the delivery system to transport the cargos inside targeted cells. However, limited studies have been conducted to verify the integrity of cargo/carrier nanocomplexes and their capability in facilitating cargo delivery intracellularly after the nanocomplex crossing the epithelial barrier. Herein, we used a traditional 2D transwell system and a recently developed 3D tissue engineered intestine model and demonstrated the synthetic lipid nanoparticle (carrier) and protein (cargo) nanocomplexes are able to cross the epithelial layer and deliver the protein cargo inside the underneath cells. We found that the EC16-63 LNP efficiently encapsulated the GFP-Cre recombinase, penetrated the intestinal monolayer cells in both the 2D cell culture and 3D tissue models through temporarily interrupting the tight junctions between epithelial layer. After transporting across the intestinal epithelia, the EC16-63 and GFP-Cre recombinase nanocomplexes can enter the underneath cells to induce gene recombination. These results suggest that the in vitro 3D intestinal tissue model is useful for identifying effective lipid nanoparticles for potential oral drug delivery.
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spelling pubmed-80561822021-04-23 Study the lipidoid nanoparticle mediated genome editing protein delivery using 3D intestinal tissue model Yang, Tao Han, Haobo Chen, Ying Yang, Liu Parker, Rachael Li, Yamin Kaplan, David L. Xu, Qiaobing Bioact Mater Article Lipid nanoparticles are promising carriers for oral drug delivery. For bioactive cargos with intracellular targets, e.g. gene-editing proteins, it is essential for the cargo and carrier to remain complexed after crossing the epithelial layer of intestine in order for the delivery system to transport the cargos inside targeted cells. However, limited studies have been conducted to verify the integrity of cargo/carrier nanocomplexes and their capability in facilitating cargo delivery intracellularly after the nanocomplex crossing the epithelial barrier. Herein, we used a traditional 2D transwell system and a recently developed 3D tissue engineered intestine model and demonstrated the synthetic lipid nanoparticle (carrier) and protein (cargo) nanocomplexes are able to cross the epithelial layer and deliver the protein cargo inside the underneath cells. We found that the EC16-63 LNP efficiently encapsulated the GFP-Cre recombinase, penetrated the intestinal monolayer cells in both the 2D cell culture and 3D tissue models through temporarily interrupting the tight junctions between epithelial layer. After transporting across the intestinal epithelia, the EC16-63 and GFP-Cre recombinase nanocomplexes can enter the underneath cells to induce gene recombination. These results suggest that the in vitro 3D intestinal tissue model is useful for identifying effective lipid nanoparticles for potential oral drug delivery. KeAi Publishing 2021-04-06 /pmc/articles/PMC8056182/ /pubmed/33898871 http://dx.doi.org/10.1016/j.bioactmat.2021.03.027 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Yang, Tao
Han, Haobo
Chen, Ying
Yang, Liu
Parker, Rachael
Li, Yamin
Kaplan, David L.
Xu, Qiaobing
Study the lipidoid nanoparticle mediated genome editing protein delivery using 3D intestinal tissue model
title Study the lipidoid nanoparticle mediated genome editing protein delivery using 3D intestinal tissue model
title_full Study the lipidoid nanoparticle mediated genome editing protein delivery using 3D intestinal tissue model
title_fullStr Study the lipidoid nanoparticle mediated genome editing protein delivery using 3D intestinal tissue model
title_full_unstemmed Study the lipidoid nanoparticle mediated genome editing protein delivery using 3D intestinal tissue model
title_short Study the lipidoid nanoparticle mediated genome editing protein delivery using 3D intestinal tissue model
title_sort study the lipidoid nanoparticle mediated genome editing protein delivery using 3d intestinal tissue model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056182/
https://www.ncbi.nlm.nih.gov/pubmed/33898871
http://dx.doi.org/10.1016/j.bioactmat.2021.03.027
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