



@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; 
Chollet, P., Favrot, M.C., Hurbin, A., Coll, J.L., Side-effects of a systemic injection of linear polyethylenimine-DNA complexes (2002) J Gene Med, 4, pp. 84-91; 
Shi, C., Zhu, Y., Ran, X., Wang, M., Su, Y., Cheng, T., Therapeutic potential of chitosan and its derivatives in regenerative medicine (2006) J Surg Res, 133, pp. 185-192; 
Mansouri, S., Lavigne, P., Corsi, K., Benderdour, M., Beaumont, E., Fernandes, J.C., Chitosan-DNA nanoparticles as non-viral vectors in gene therapy: Strategies to improve transfection efficacy (2004) Eur J Pharm Biopharm, 57, pp. 1-8; 
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; 
Verma, A., Stellacci, F., Effect of surface properties on nanoparticle-cell interactions (2010) Small, 6, pp. 12-21; 
Brugnerotto, J., Lizardi, J., Goycoolea, F.M., Arguelles-Monal, W., Desbrieres, J., Rinaudo, M., An infrared investigation in relation with chitin and chitosan characterization (2001) Polymer, 42, pp. 3569-3580; 
(1987) Guideline on Validation of the Limulus Amebocyte Lysate Test As An End-product Endotoxin Test for Human and Animal Parental Drugs, Biological Products, and Medical Devices, , US Department of Health and Human Services. US Department of Health and Human Services; 
MacUlotti, K., Genta, I., Perugini, P., Imam, M., Bernkop-Schnurch, A., Pavanetto, F., Preparation and in vitro evaluation of thiolated chitosan microparticles (2005) J Microencapsul, 22, pp. 459-470; 
Mao, H., Roy, K., Troung-Le, V.L., Janes, K.A., Lin, K.Y., Wang, Y., August, J.T., Leong, K.W., Chitosan-DNA nanoparticles as gene carriers: Synthesis, characterization and transfection efficiency (2001) J Control Release, 70, pp. 399-421; 
Innes, N.P.T., Ogden, G.R., A technique for the study of endocytosis in human oral epithelial cells (1999) Arch Oral Biol, 44, pp. 519-523; 
O{\textquoteright}Brien, J., Wilson, I., Orton, T., Pognan, F., Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity (2000) Eur J Biochem, 267, pp. 5421-5426; 
Ellman, G.L., Tissue sulfhydryl groups (1959) Arch Biochem Biophys, 82, pp. 70-77; 
Lee, D., Zhang, W., Shirley, S.A., Kong, X., Hellermann, G.R., Lockey, R.F., Mohapatra, S.S., Thiolated chitosan/DNA nanocomplexes exhibit enhanced and sustained gene delivery (2007) Pharm Res, 24, pp. 157-167; 
Loretz, B., Thaler, M., Bernkop-Schnurch, A., Role of sulfhydryl groups in transfection? A case study with chitosan-NAC nanoparticles (2007) Bioconjug Chem, 18, pp. 1028-1035; 
Deinhardt, K., Berninghausen, O., Willison, H.J., Hopkins, C.R., Schiavo, G., Tetanus toxin is internalized by a sequential clathrin-dependent mechanism initiated within lipid microdomains and independent of epsin 1 (2006) J Cell Biol, 174, pp. 459-471; 
Williamson, L.C., Neale, E.A., Bafilomycin A1 inhibits the action of tetanus toxin in spinal-cord neurons in cell-culture (1994) J Neurochem, 63, pp. 2342-2345; 
Bohnert, S., Schiavo, G., Tetanus toxin is transported in a novel neuronal compartment characterized by a specialized pH regulation (2005) J Biol Chem, 280, pp. 42336-42344
},
	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.}
}
