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- W1900685089 abstract "Abstract Clinical translation of siRNA therapeutics has been limited by the inability to effectively overcome the rigorous delivery barriers associated with intracellular‐acting biologics. Here, to address both potency and longevity of siRNA gene silencing, pH‐responsive micellar nanoparticle (NP) carriers loaded with siRNA conjugated to palmitic acid (siRNA‐PA) were investigated as a combined approach to improve siRNA endosomal escape and stability. Conjugation to hydrophobic PA improved NP loading efficiency relative to unmodified siRNA, enabling complete packaging of siRNA‐PA at a lower polymer:siRNA ratio. PA conjugation also increased intracellular uptake of the nucleic acid cargo by 35‐fold and produced a 3.1‐fold increase in intracellular half‐life. The higher uptake and improved retention of siRNA‐PA NPs correlated to a 2‐ and 11‐fold decrease in gene silencing IC 50 in comparison to siRNA NPs in fibroblasts and mesenchymal stem cells, respectively, for both the model gene luciferase and the therapeutically relevant gene prolyl hydroxylase domain protein 2 (PHD2) . PA conjugation also significantly increased longevity of silencing activity following a single treatment in fibroblasts. Thus, conjugation of PA to siRNA paired with endosomolytic NPs is a promising approach to enhance the functional efficacy of siRNA in tissue regenerative and other applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3107–3116, 2015." @default.
- W1900685089 created "2016-06-24" @default.
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- W1900685089 date "2015-02-27" @default.
- W1900685089 modified "2023-10-16" @default.
- W1900685089 title "Conjugation of palmitic acid improves potency and longevity of siRNA delivered via endosomolytic polymer nanoparticles" @default.
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- W1900685089 doi "https://doi.org/10.1002/jbm.a.35413" @default.
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