| Title | Targeted gene delivery into peripheral sensorial neurons mediated by self-assembled vectors composed of poly(ethylene imine) and tetanus toxin fragment c |
| Publication Type | Journal Article |
| 2010 |
| Authors | Oliveira, H, Fernandez, R, Pires, LR, Martins, MCL, Simões, S, Barbosa, MA, Pêgo, AP |
| Journal | Journal of Controlled ReleaseJ. Control. Release |
| Volume | 143 |
| Issue | 3 |
| Pagination | 350 - 358 |
| Date Published | 2010/// |
| 01683659 (ISSN) |
| Aberrations, animal cell, Animals, article, Bifunctional, Cell culture, Cell Line, Tumor, Cell lines, cell strain 3T3, Cells, Cultured, Cellular internalization, Chemical modification, Complex cores, Complex formulations, Complex surface, controlled study, DNA, DNA protein complex, Dorsal root ganglia, Efficient systems, embryo, Ethylene, Female, Gene transfer, genetic transfection, Imines, internalization, macrogol, Mice, mouse, Multicomponents, nanoparticle, nanoparticles, neuroblastoma cell, Neuronal cell, Neurons, neurotrophic factor, Neurotrophic factors, NIH 3T3 Cells, Nitrogen compounds, Non-viral, Non-viral gene delivery, nonhuman, Nonviral, nonviral gene delivery system, Nucleic acids, Particle Size, Peptide Fragments, Peripheral nervous system, Peripheral neuropathy, Plasmids, Polyethylene Glycols, Polyethylene oxides, Polyethyleneimine, Polyethylenes, Primary culture, priority journal, process optimization, protein expression, rat, Rats, Rats, Wistar, Regenerative Medicine, Self-assembled, sensory nerve cell, spinal ganglion, Starting materials, Targeted, Targeted gene delivery, Ternary complex, Ternary vectors, Tetanus toxin, tetanus toxin fragment c, Transfection, unclassified drug, Zeta potential |
| 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. Μg 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. © 2010 Elsevier B.V. |
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