Wan Yu, Moyle Peter M, Christie Michelle P, Toth Istvan
School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia, 4072, QLD, Australia.
School of Pharmacy, The University of Queensland, Woolloongabba, 4102, QLD, Australia.
Nanomedicine (Lond). 2016 Apr;11(8):907-19. doi: 10.2217/nnm.16.27. Epub 2016 Mar 16.
Endosome escape is essential for developing effective nonviral gene delivery systems. Herein, three endosome-disrupting peptides (HA2(1-20), GALA and KALA) were incorporated into a multicomponent oligonucleotide delivery system to identify which peptide imparted the most favorable endosome escape and toxicity profile.
MATERIALS & METHODS: Copper (I)-catalyzed azide-alkyne cycloaddition was used to construct multicomponent delivery vectors. The systems were evaluated for size, toxicity, cellular uptake and endosome escape activity.
Each system condensed plasmid DNA to form nanosized particles. The highest cellular uptake and endosome escape were associated with GALA and KALA containing systems, with KALA incorporation correlating with greater toxicity.
GALA was selected as the most promising endosome-disrupting peptide for incorporation into the nanosized oligonucleotide delivery system.
内体逃逸对于开发有效的非病毒基因递送系统至关重要。在此，将三种内体破坏肽（HA2(1-20)、GALA和KALA）整合到多组分寡核苷酸递送系统中，以确定哪种肽具有最有利的内体逃逸和毒性特征。
使用铜（I）催化的叠氮化物-炔烃环加成反应构建多组分递送载体。对这些系统进行了尺寸、毒性、细胞摄取和内体逃逸活性评估。
每个系统都能凝聚质粒DNA形成纳米颗粒。最高的细胞摄取和内体逃逸与含有GALA和KALA的系统相关，KALA的整合与更大的毒性相关。
GALA被选为最有前景的内体破坏肽，可整合到纳米级寡核苷酸递送系统中。
