期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 458, 期 1, 页码 48-56出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2013.10.017
关键词
Glioma targeting; C-end rule peptide; Neuropilin-1; Gene delivery; Polyethylenimine
资金
- National Key Basic Research Program of China [2013CB932502, 2010CB934000]
- National Science and Technology Major Project [2012ZX09304004]
- National Science Foundation of China [30772655, 81202471]
- Foundation Program of the Key Laboratory of Smart Drug Delivery of the Ministry of Education [SDD2011-03]
Safe and efficient systems capable of specifically targeting brain tumour cells represent a promising approach for the treatment glioblastoma multiforme. Neuropilin-1 (NRP-1) is over-expressed in U87 glioma cells. In the current study, the tumour specific peptide RGERPPR, which binds specifically to NRP-1, was used as a targeting ligand in a gene delivery strategy for glioblastoma. The RGERPPR peptide was coupled to branched polyethylenimine (PEI, 25 kDa) using heterobifunctional Mal-PEG-NHS, resulting in a novel gene delivery polymer. Polymer/plasmid DNA (pDNA) complexes were formed and their sizes and zeta potentials were measured. Compared with the unmodified mPEG-PEI/pDNA complexes, the RGERPPR-PEG-PEI/pDNA complex led to a significant enhancement in intracellular gene uptake and tumour spheroid penetration. Furthermore, the RGERPPR-PEG-PEI/pDNA complex facilitated enhanced transfection efficiency levels, as well as a reduction in cytotoxicity when tested in U87 glioma cells in vitro. Most significantly of all, when complexes formed with pDsRED-N1 were injected into the tail vein of intracranial U87 tumour-bearing nude mice, the RGERPPR-PEG-PEI complexes led to improved levels of red fluorescence protein expression in the brain tissue. Taken together, the results show that RGERPPR-PEG-PEI could be used as a safe and efficient gene delivery vehicle with potential applications in glioblastoma gene delivery. (C) 2013 Elsevier B.V. All rights reserved.
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