



@article {2244,
	title = {Chitosan-based gene delivery vectors targeted to the peripheral nervous system},
	journal = {Journal of Biomedical Materials Research - Part AJ. Biomed. Mater. Res. Part A},
	volume = {95},
	year = {2010},
	note = {Cited By (since 1996): 5Export Date: 21 November 2012Source: ScopusCODEN: JBMRCdoi: 10.1002/jbm.a.32874PubMed ID: 20734332Language of Original Document: EnglishCorrespondence Address: P{\^e}go, A. P.; INEB, Instituto de Engenharia Biom{\'e}dica, Universidade Do Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; email: apego@ineb.up.ptChemicals/CAS: DNA, 9007-49-2; chitosan, 9012-76-4; imidazole, 1467-16-9, 288-32-4; macrogol, 25322-68-3; Cations; Chitosan, 9012-76-4; DNA, 9007-49-2; Polyethylene GlycolsTradenames: Chimarin, medicarb, SwedenManufacturers: medicarb, SwedenReferences: Rodriguez, F.J., Valero-Cabre, A., Navarro, X., Regeneration and functional recovery following peripheral nerve injury (2004) Drug Discov Today, 1, pp. 177-185;Apfel, S.C., Neurotrophic factors in peripheral neuropathies: Therapeutic implications (1999) Brain Pathol, 9, pp. 393-413; 
Apfel, S.C., Is the therapeutic application of neurotrophic factors dead? (2002) Ann Neurol, 51, pp. 8-11; 
Glorioso, J.C., Mata, M., Fink, D.J., Therapeutic gene transfer to the nervous system using viral vectors (2003) J Neurovirol, 9, pp. 165-172; 
Fishman, P.S., Carrigan, D.R., Retrograde transneuronal transfer of the C-fragment of tetanus toxin (1987) Brain Res, 406, pp. 275-279; 
Evinger, C., Erichsen, J.T., Transsynaptic retrograde transport of fragment C of tetanus toxin demonstrated by immunohistochemical localization (1986) Brain Res, 380, pp. 383-388; 
Figueiredo, D.M., Hallewell, R.A., Chen, L.L., Fairweather, N.F., Dougan, G., Savitt, J.M., Parks, D.A., Fishman, P.S., Delivery of recombinant tetanus-superoxide dismutase proteins to central nervous system neurons by retrograde axonal transport (1997) Exp Neurol, 145 (2 PART 1), pp. 546-554; 
Fishman, P.S., Savitt, J.M., Farrand, D.A., Enhanced CNS uptake of systemically administered proteins through conjugation with tetanus C-fragment (1990) J Neurol Sci, 98, pp. 311-325; 
Coen, L., Osta, R., Maury, M., Brulet, P., Construction of hybrid proteins that migrate retrogradely and transynaptically into the central nervous system (1997) Proc Natl Acad Sci USA, 94, pp. 9400-9405; 
Knight, A., Carvajal, J., Schneider, H., Coutelle, C., Chamberlain, S., Fairweather, N., Non-viral neuronal gene delivery mediated by the HC fragment of tetanus toxin (1999) Eur J Biochem, 259, pp. 762-769; 
Oliveira, H., Fernandez, R., Pires, L.R., Sim{\~o}es, S., Martins, M.C.L., Barbosa, M.A., P{\^e}go, A.P., Targeted gene delivery into peripheral sensorial neurons mediated by self-assembled vectors composed of poly(ethilenimine) and tetanus toxin fragment c (2010) J Control Release, 143, pp. 350-358; 
Neu, M., Fischer, D., Kissel, T., Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives (2005) J Gene Med, 7, pp. 992-1009; 
Tang, G.P., Guo, H.Y., Alexis, F., Wang, X., Zeng, S., Lim, T.M., Ding, J., Wang, S., Low molecular weight polyethylenimines linked by beta-cyclodextrin for gene transfer into the nervous system (2006) J Gene Med, 8, pp. 736-744; 
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Moreira, C., Oliveira, H., Pires, L.R., Simoes, S., Barbosa, M.A., Pego, A.P., Improving chitosan-mediated gene transfer by the introduction of intracellular buffering moieties into the chitosan backbone (2009) Acta Biomater, 5, pp. 2995-3006; 
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},
	month = {2010///},
	pages = {801 - 810},
	abstract = {A non-toxic, targeted, simple and efficient system that can specifically transfect peripheral sensorial neurons can pave the way towards the development of new therapeutics for the treatment of peripheral neuropathies. In this study chitosan (CH), a biodegradable polymer, was used as the starting material in the design of a multicomponent vector targeted to the peripheral nervous system (PNS). Polycation-DNA complexes were optimized using imidazole-and thiol-grafted CH (CHimiSH), in order to increase transfection efficiency and allow the formation of ligand conjugated nanocomplexes, respectively. The 50 kDa non-toxic fragment from the tetanus toxin (HC), shown to interact specifically with peripheral neurons and undergo retrograde transport, was grafted to the binary complex via a bi-functional poly(ethylene glycol) (HC-PEG) reactive for the thiol moieties present in the complex surface. The targeting of the developed nanocomplexes was assessed by means of internalization and transfection studies in the ND7/23 (neuronal) vs. NIH 3T3 (fibroblast) cell lines. Targeted transfection was further confirmed in dorsal root ganglion dissociated primary cultures. A versatile, multi-component nanoparticle system that successfully targets and transfects neuronal cell lines, as well as dorsal root ganglia (DRG) primary neuron cultures was obtained for the 1.0 (w/w) HC-PEG/DNA formulation. {\textcopyright} 2010 Wiley Periodicals, Inc.},
	keywords = {animal cell, Animals, article, Binary complexes, Biodegradable polymers, Carbohydrate Conformation, Carbohydrate Sequence, Cations, Cell culture, Cell lines, cell population, Cells, Cultured, Chitin, chitosan, Complex surface, DNA, DNA complex, Dorsal root ganglia, Efficient systems, embryo, Ethylene, Ethylene Glycol, Female, Ganglia, Spinal, Gene delivery, gene delivery system, Gene delivery vectors, Gene therapy, Gene transfer, Gene Transfer Techniques, genetic transfection, Genetic Vectors, Grafting (chemical), Humans, imidazole, macrogol, materials testing, Mice, Molecular Sequence Data, Molecular Structure, mouse, Multicomponents, Nanocomplexes, Nanoparticle systems, nanoparticles, nerve cell culture, Neuron culture, Neuronal cell, NIH 3T3 Cells, nonhuman, Nontoxic fragment of tetanus toxin, Peripheral nervous system, Peripheral neuropathy, Polycations, Polyethylene Glycols, Polyethylene oxides, Pregnancy, Primary culture, rat, Rats, Rats, Wistar, spinal ganglion, Starting materials, Targeted, Tetanus toxin, Toxic materials, Transfection, Transfection efficiency},
	isbn = {15493296 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-78249240032\&partnerID=40\&md5=af9c3ca5ca712d53abb5e80f45ed09c0},
	author = {Oliveira, H. and Pires, L.R. and Fernandez, R. and Martins, M.C.L. and Sim{\~o}es, S. and P{\^e}go, A.P.}
}
@article {2275,
	title = {Targeted gene delivery into peripheral sensorial neurons mediated by self-assembled vectors composed of poly(ethylene imine) and tetanus toxin fragment c},
	journal = {Journal of Controlled ReleaseJ. Control. Release},
	volume = {143},
	year = {2010},
	note = {Cited By (since 1996): 13Export Date: 21 November 2012Source: ScopusCODEN: JCREEdoi: 10.1016/j.jconrel.2010.01.018PubMed ID: 20093157Language of Original Document: EnglishCorrespondence Address: P{\^e}go, A.P.; INEB-Instituto de Engenharia Biom{\'e}dica, Divis{\~a}o de Biomateriais, Universidade do Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; email: apego@ineb.up.ptChemicals/CAS: DNA, 9007-49-2; macrogol, 25322-68-3; polyethyleneimine, 74913-72-7; DNA, 9007-49-2; Imines; Peptide Fragments; Polyethylenes; Tetanus Toxin; poly(ethylene imine); tetanus toxin fragment CReferences: Rodriguez, F.J., Valero-Cabre, A., Navarro, X., Regeneration and functional recovery following peripheral nerve injury (2004) Drug Discov. Today, 1 (2), pp. 177-185;Sahenk, Z., Neurotrophins and peripheral neuropathies (2006) Brain Pathol., 16 (4), pp. 311-319; 
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},
	month = {2010///},
	pages = {350 - 358},
	abstract = {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. {\textcopyright} 2010 Elsevier B.V.},
	keywords = {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},
	isbn = {01683659 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-77952239026\&partnerID=40\&md5=077b03d49cf392defc3d0c77f2f249d1},
	author = {Oliveira, H. and Fernandez, R. and Pires, L.R. and Martins, M.C.L. and Sim{\~o}es, S. and Barbosa, M.A. and P{\^e}go, A.P.}
}
@article {2296,
	title = {Improving chitosan-mediated gene transfer by the introduction of intracellular buffering moieties into the chitosan backbone},
	journal = {Acta BiomaterialiaActa Biomater.},
	volume = {5},
	year = {2009},
	note = {Cited By (since 1996): 17Export Date: 21 November 2012Source: Scopusdoi: 10.1016/j.actbio.2009.04.021PubMed ID: 19427930Language of Original Document: EnglishCorrespondence Address: P{\^e}go, A.P.; INEB-Instituto de Engenharia Biom{\'e}dica, Divis{\~a}o de Biomateriais, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal; email: apego@ineb.up.ptChemicals/CAS: DNA, 9007-49-2; chitosan, 9012-76-4; imidazole, 1467-16-9, 288-32-4; Biocompatible Materials; Buffers; Chitosan, 9012-76-4; DNA, 9007-49-2; Drug CarriersReferences: Kirkpatrick, C.J., Fuchs, S., Peters, K., Brochhausen, C., Hermanns, M.I., Unger, R.E., Visions for regenerative medicine: interface between scientific fact and science fiction (2006) Artif Organs, 30, pp. 822-827;Sim{\~o}es, S., Filipe, A., Faneca, H., Mano, M., Penacho, N., Duzgunes, N., Cationic liposomes for gene delivery (2005) Expert Opin Drug Deliv, 2, pp. 237-254; 
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},
	month = {2009///},
	pages = {2995 - 3006},
	abstract = {Chitosan was functionalized with imidazole moieties (CHimi) with the aim of improving its buffering capacity and promoting the endosomal escape ability of chitosan-DNA complexes, ultimately increasing their transfection efficiency. 5.6\%, 12.9\% and 22.1\% of the glucosamine residues of chitosan were substituted. Complexes with different molar ratios of primary amines to DNA phosphate anion (N/P) were prepared by a coacervation method. For an N/P \&gt; 3, CHimi polymers are able to complex electrostatically with DNA and condense it into positively charged nanostructures (average size 260 nm and zeta potential +16 mV at pH 5.5). In the concentration range 2.5-100 μg ml},
	keywords = {article, beta galactosidase, Biocompatible Materials, Buffers, Cell Line, cell transport, Chemical structure, chitosan, coacervation, complex formation, controlled study, Cytotoxicity, Diffusion, DNA, Drug Carriers, Drug Compounding, endosome, Gene delivery, Gene transfer, genetic transfection, human, human cell, Humans, imidazole, Kidney, materials testing, nanomaterial, nanoparticle, priority journal, protein expression, proton transport, Tissue engineering, Transfection},
	isbn = {17427061 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-70349162856\&partnerID=40\&md5=fb6672dd0cf06d6ced21eec115b597d2},
	author = {Moreira, C. and Oliveira, H. and Pires, L.R. and Sim{\~o}es, S. and Barbosa, M.A. and P{\^e}go, A.P.}
}
