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

Bioactive Materials 2021年第11期6卷 3671-3677页

作者： Tao Yang Haobo Han Ying Chen Liu Yang Rachael Parker Yamin Li David L.Kaplan Qiaobing Xu Department of Biomedical Engineering Tufts UniversityMedfordMAUSA Department of Prosthodontics Guanghua School of StomatologyHospital of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhou510055China Key Laboratory for Molecular Enzymology1nd Engineering of Ministry of Education School of Life SciencesJilin UniversityChangchun130012China

Lipid nanoparticles are promising carriers for oral drug *** bioactive cargos with intracellular targets,***-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 ***,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 ***,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 *** 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 *** transporting across the intestinal epithelia,the EC16-63 and GFP-Cre recombinase nanocomplexes can enter the underneath cells to induce gene *** results suggest that the in vitro 3D intestinal tissue model is useful for identifying effective lipid nanoparticles for potential oral drug delivery.

关键词： lipidoid nanoparticle Protein delivery Oral drug delivery Genome engineering 3D tissue model

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