Gastrin-releasing peptide receptor-targeted hybrid peptide/phospholipid pDNA/siRNA delivery systems

被引:6
作者
Begum, Anjuman A. [1 ,2 ]
Toth, Istvan [1 ,2 ,3 ]
Moyle, Peter M. [2 ]
机构
[1] Univ Queensland, SCMB, St Lucia, Qld 4072, Australia
[2] Univ Queensland, Sch Pharm, Woolloongabba, Qld 4102, Australia
[3] Univ Queensland, IMB, St Lucia, Qld 4072, Australia
基金
英国医学研究理事会; 澳大利亚研究理事会;
关键词
DNA delivery; gastrin-releasing peptide receptor; nonviral vectors; peptide-based delivery; prostate cancer; siRNA delivery; CELL-PENETRATING PEPTIDES; PROSTATE-CANCER CELLS; GENE DELIVERY; NONVIRAL VECTORS; EFFICIENT; SIRNA; DNA; COMPLEXES; LIPOSOME; NANOCOMPLEXES;
D O I
10.2217/nnm-2018-0380
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Aim: To develop a peptide/phospholipid hybrid system for gastrin-releasing peptide receptor (GRPR)-targeted delivery of pDNA or siRNA. Materials & methods: A multifunctional GRPR-targeted peptide R-9-K(GALA)-BBN(6-14) was combined with a phospholipid oligonucleotide delivery system (1:1 1,2-dioleoyl-sn-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. Results: 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. Conclusion: The peptide/phospholipid hybrid system provides efficient GRPR-targeted DNA/siRNA delivery.
引用
收藏
页码:1153 / 1171
页数:19
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