School of Chemistry & Molecular Biosciences (SCMB), The University of Queensland, St Lucia 4072, Australia.
School of Pharmacy, The University of Queensland, Woolloongabba 4102, Australia.
Nanomedicine (Lond). 2019 May;14(9):1153-1171. doi: 10.2217/nnm-2018-0380. Epub 2019 May 3.
To develop a peptide/phospholipid hybrid system for gastrin-releasing peptide receptor (GRPR)-targeted delivery of pDNA or siRNA. A multifunctional GRPR-targeted peptide R-K(GALA)-BBN(6-14) was combined with a phospholipid oligonucleotide delivery system (1:1 1,2-dioleoyl--glycero-3-phosphoethanolamine and 1,2-dioleoyl-3-trimethylammonium-propane) and evaluated for pDNA and siRNA delivery in terms of complex size, toxicity, receptor-targeted delivery and gene expression or knockdown efficiency. By combining peptide and phospholipid delivery systems, synergistic improvements in gene expression and knockdown were observed when compared with either system alone. The optimized formulation demonstrated high levels of EGFP expression and EGFP knockdown, GRPR-targeted delivery, enhanced endosomal release and minimal toxicity. The peptide/phospholipid hybrid system provides efficient GRPR-targeted DNA/siRNA delivery.
为了开发一种用于胃泌素释放肽受体（GRPR）靶向递送 pDNA 或 siRNA 的肽/磷脂混合系统。将多功能 GRPR 靶向肽 R-K（GALA）-BBN（6-14）与磷脂寡核苷酸递送系统（1:1 1,2-二油酰基-甘油-3-磷酸乙醇胺和 1,2-二油酰基-3-三甲基铵丙烷）结合，并评估其在 pDNA 和 siRNA 递送方面的复合物大小、毒性、受体靶向递送以及基因表达或敲低效率。通过结合肽和磷脂递送系统，与单独使用任何一种系统相比，观察到基因表达和敲低的协同改善。优化的配方表现出高水平的 EGFP 表达和 EGFP 敲低、GRPR 靶向递送、增强的内体释放和最小的毒性。肽/磷脂混合系统提供了高效的 GRPR 靶向 DNA/siRNA 递送。
