Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 10, Issue 3, Pages 525-534Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2013.10.005
Keywords
Gene delivery; Endosomal escape; Osmolysis; Proton sponge; Polyethylenimine
Funding
- National Research Foundation of Korea [NRF-2012-0003119]
- Cooperative Research Program for Agriculture Science and Technology Development [PJ007611]
- Rural Development Administration, Republic of Korea
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Endosomal escape is one of the important processes for efficient non-viral gene delivery. In this study, we synthesized a novel non-viral vector called polyxylitol-based gene carrier (XGC) through a Miachael addition reaction between xylitol diacrylate as a crosslinking agent and low molecular weight polyethylenimine (PEI 1.2 kDa). The small amount of xylitol integrated into XGC (3.9% w/w) contributed 50% of the osmotic pressure of XGC, and enhaned the osmolysis of endosome cooperatively with the proton sponge effect, thus improving endosomal escape. Furthermore, XGC showed higher transfection efficiency in vivo in muscle tissue than pDNA alone or PEI 25 kDa. In conclusion, our results show that XGC enhanced transfection efficiency compared with PEI 25 kDa, the golden standard non-viral gene carrier, by enhancing endosomal escape without increasing the number of transfected cells. From the Clinical Editor: Enhanced gene delivery methods would greatly facilitate the development of gene therapies. These authors demonstrate that a polyxylitol-based gene carrier enhanced the transfection efficiency compared with the gold standard non-viral gene carrier, as a result of enhancing endosomal escape without increasing the number of transfected cells, warranting further studies of this method. (C) 2014 Elsevier Inc. All rights reserved.
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