期刊
JOURNAL OF CONTROLLED RELEASE
卷 143, 期 3, 页码 350-358出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2010.01.018
关键词
Peripheral nervous system; Non-viral; Nanoparticle; Targeted; Regenerative medicine
资金
- Portuguese Foundation for Science and Technology (FCT) [POCI/SAU-BMA/58170/2004]
- FCT [SFRH/BD/22090/2005, SFRH/BD/46015/2008]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/46015/2008, POCI/SAU-BMA/58170/2004, SFRH/BD/22090/2005] Funding Source: FCT
A simple, safe and efficient system that can specifically transfect peripheral sensorial neurons can bring new answers to address peripheral neuropathies. A multi-component non-viral gene delivery vector targeted to peripheral nervous system cells was developed, using poly(ethylene imine) (PEI) as starting material. A binary DNA/polymer complex based on thiolated PEI (PEISH) was optimized, considering complex size and zeta potential and the ability to transfect a sensorial neuron cell line (ND7/23). The 50 kDa non-toxic fragment from tetanus toxin (HC), which has been previously shown to interact specifically with peripheral neurons and to undergo retrograde transport, was grafted to the complex core via a bifunctional PEG (HC-PEG) reactive for the thiol moieties present in the complex surface. Several formulations of HC-PEG ternary complexes were tested for targeting, by assessing the extent of cellular internalization and levels of transfection, in both the ND7/23 and NIH 3 T3 (fibroblast) cell lines. Targeted gene transfer to the neuronal cell line was observed for the complex formulations containing 5 and 7.5 mu g of HC-PEG. Finally, our results demonstrate that the developed ternary vectors are able to transfect primary cultures of dorsal root ganglion dissociated neurons in a targeted manner and elicit the expression of a relevant neurotrophic factor. (C) 2010 Elsevier B.V. All rights reserved.
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