



@article {2196,
	title = {A novel nanoparticle delivery system for in vivo targeting of the sciatic nerve: Impact on regeneration},
	journal = {NanomedicineNanomedicine},
	volume = {7},
	year = {2012},
	note = {Export Date: 21 November 2012Source: Scopusdoi: 10.2217/nnm.11.188Language of Original Document: EnglishCorrespondence Address: Saraiva, M.J.; Unidade de Neurobiologia Molecular, IBMC-Instituto de Biologia Molecular e Celular, 4150-180 Porto, Portugal; email: mjsaraiv@ibmc.up.ptReferences: Rodriguez, F.J., Valero-Cabre, A., Navarro, X., Regeneration and functional recovery following peripheral nerve injury (2004) Drug Discovery Today: Disease Models, 1 (2), pp. 177-185. , DOI 10.1016/j.ddmod.2004.09.008;Apfel, S.C., Neurotrophic factors in peripheral neuropathies: Therapeutic implications (1999) Brain Pathology, 9 (2), pp. 393-413; 
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},
	month = {2012///},
	pages = {1167 - 1180},
	abstract = {Aim: Innovative solutions in the development of drug delivery systems targeting the nerve tissue are awaited. In this regard, a novel system for the delivery of drugs to the sciatic nerve was created using nanomedical principles. Materials \& methods: Chitosan was the vehicle material used in the experiment. Heparin bound to growth factors has been administered to enhance peripheral nerve regeneration, and since heparin possesses the appropriate charge to be able to form nanoparticles with chitosan, it appears to be a good candidate to base this new delivery system on. Results: Maximal absorption took place throughout the extracellular matrix at day 15. No major inflammatory response was observed, indicating that this is a safe and biocompatible system for drug delivery to nerves. Sensorimotor performance and nerve regeneration of mice receiving these nanoparticles were superior as compared with controls. Conclusion: Our work demonstrates a versatile nanoparticle delivery system that successfully targets drugs {\textquoteright}in vivo to the sciatic nerve, opening novel avenues in the field of nanomedicine to the design of therapeutic strategies that enhance axonal regeneration. {\textcopyright} 2012 Future Medicine Ltd.},
	keywords = {chitosan, drug delivery system, heparin, nanomedicine, nanoparticles, peripheral nerve regeneration, sciatic nerve},
	isbn = {17435889 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84868111412\&partnerID=40\&md5=5db0c76b3a921ca70565c9f3f63cf004},
	author = {Gon{\c c}alves, N.P. and Oliveira, H. and P{\^e}go, A.P. and Saraiva, M.J.}
}
@article {2231,
	title = {Molecular recognition force spectroscopy: A new tool to tailor targeted nanoparticles},
	journal = {SmallSmall},
	volume = {7},
	year = {2011},
	note = {Cited By (since 1996): 1Export Date: 21 November 2012Source: Scopusdoi: 10.1002/smll.201002074Language of Original Document: EnglishCorrespondence Address: P{\^e}go, A. P.; INEB-Instituto de Engenharia Biom{\'e}dica, Divis̃o de Biomateriais, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal; email: apego@ineb.up.ptReferences: Verma, I.M., Weitzman, M.D., (2005) Annu. Rev. Biochem., 74, pp. 711-738;Midoux, P., Breuzard, G., Gomez, J.P., Pichon, C., (2008) Curr. Gene Ther., 8, pp. 335-352; 
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},
	month = {2011///},
	pages = {1236 - 1241},
	abstract = {The density of targeting moieties in a nanoparticle-based gene-delivery system has been shown to play a fundamental role in its vectoring performance. Here, molecular recognition force spectroscopy is proposed as a novel screening tool to optimize the density of targeting moieties of functionalized nanoparticles towards attaining cell-specific interaction. By tailoring the nanoparticle formulation, the unbinding event probability between nanoparticles tethered to an atomic force microscopy tip and neuronal cells is directly correlated to the nanoparticle gene-vectoring capacity. Additionally, new insights into protein-receptor interaction are revealed. This novel approach opens new avenues in the field of nanomedicine. A novel screening tool is described to optimize the density of targeting moieties of functionalized nanoparticles towards attaining cell-specific interaction. The unbinding event probability between nanoparticles tethered to an atomic force microscopy tip and neuronal cells is directly correlated to the nanoparticle gene-vectoring capacity. {\textcopyright} 2011 WILEY-VCH Verlag GmbH \& Co. KGaA, Weinheim.},
	keywords = {article, Atomic force microscopy, Atomic spectroscopy, atomic-force microscopy, chemistry, Event probability, Force spectroscopy, Functionalized nanoparticles, gene technology, Gene-delivery systems, Genes, Medical nanotechnology, medicine, methodology, Microscopy, Atomic Force, Molecular biology, Molecular recognition, molecular recognition force spectroscopy, Nanomedicines, nanoparticle, Nanoparticle formulation, nanoparticles, Nanotechnology, Neuronal cell, Optimization, Receptor interaction, Screening tool, Specific interaction, Targeted nanoparticle},
	isbn = {16136810 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-79955561627\&partnerID=40\&md5=85fa523edfcd7a6e171a53820be7f230},
	author = {Oliveira, H. and Rangl, M. and Ebner, A. and Mayer, B. and Hinterdorfer, P. and P{\^e}go, A.P.}
}
@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; 
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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 {2250,
	title = {Chitosan/siRNA nanoparticles biofunctionalize nerve implants and enable neurite outgrowth},
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	volume = {10},
	year = {2010},
	note = {Cited By (since 1996): 14Export Date: 21 November 2012Source: Scopusdoi: 10.1021/nl1016909Language of Original Document: EnglishCorrespondence Address: Schlosshauer, B.; NMI Natural and Medical Sciences Institute, University of T{\"u}bingen, Markwiesenstrasse 55, 72770 Reutlingen, Germany; email: schlosshauer@nmi.deChemicals/CAS: chitosan, 9012-76-4; Chitosan, 9012-76-4; RNA, Small Interfering; rhoA GTP-Binding Protein, 3.6.5.2References: Terzis, J.K., Skoulis, T.G., Soucacos, P.N., (1995) Int. Angiol., 14, pp. 264-77;Schmidt, C.E., Leach, J.B., (2003) Annu. Rev. Biomed. Eng., 5, pp. 293-347; 
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},
	month = {2010///},
	pages = {3933 - 3939},
	abstract = {Microstructured 20 μm thick polymer filaments used as nerve implants were loaded with chitosan/siRNA nanoparticles to promote nerve regeneration and ensure local delivery of nanotherapeutics. The stable nanoparticles were rapidly internalized by cells and did not affect cell viability. Target mRNA was successfully reduced by 65-75\% and neurite outgrowth was enhanced even in an inhibitory environment. This work, thus, supports the application of nanobiofunctionalized implants as a novel approach for spinal cord and nerve repair. {\textcopyright} 2010 American Chemical Society.},
	keywords = {animal, Animals, article, Cell Line, cell viability, chemistry, Chitin, chitosan, cytology, Drug delivery, genetic transfection, genetics, Local delivery, metabolism, Microstructured, nanobiofunctionalized implants, nanoparticle, nanoparticles, nerve cell, nerve regeneration, Nerve repair, neurite, Neurite outgrowth, Neurites, Neurons, Polymer filaments, Prostheses and Implants, prostheses and orthoses, rhoA GTP-Binding Protein, RhoA guanine nucleotide binding protein, RNA, RNA, Small Interfering, siRNA, small interfering RNA, Spinal cords, Transfection, ultrastructure},
	isbn = {15306984 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-77958033530\&partnerID=40\&md5=6862e82e01c3aedf5423ebb14248c6ec},
	author = {Mittnacht, U. and Hartmann, H. and Hein, S. and Oliveira, H. and Dong, M. and P{\^e}go, A.P. and Kjems, J. and Howard, K.A. and Schlosshauer, B.}
}
@article {2278,
	title = {Functionalization of poly(amidoamine) dendrimers with hydrophobic chains for improved gene delivery in mesenchymal stem cells},
	journal = {Journal of Controlled ReleaseJ. Control. Release},
	volume = {144},
	year = {2010},
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},
	month = {2010///},
	pages = {55 - 64},
	abstract = {A new family of gene delivery vectors is synthesized consisting of a medium-size generation PAMAM dendrimer (generation 5, with amine termini) core randomly linked at the periphery to hydrophobic chains that vary in length (12 to 16 carbon alkyl chains) and number (from 4.2 to 9.7 in average). The idea subjacent to the present work is to join the advantages of the cationic nature of the dendrimer with the capacity of lipids to interact with biological membranes. Unlike other amphiphilic systems designed for the same purpose, where the hydrophobic and hydrophilic moieties coexist in opposite sides, the present vectors have a hydrophilic interior and a hydrophobic corona. The vectors are characterized in respect to their ability to neutralize, bind and compact plasmid DNA (pDNA). The complexes formed between the vectors and pDNA are analyzed concerning their size, ζ-potential, resistance to serum nucleases, capacity of being internalized by cells and transfection efficiency. These new vectors show a remarkable capacity for mediating the internalization of pDNA with minimum cytotoxicity, being this effect positively correlated with the -CH                        2- content present in the hydrophobic corona. Gene expression in MSCs, a cell type with relevancy in the regenerative medicine clinical context, is also enhanced using the new vectors but, in this case, the higher efficiency is shown by the vectors containing the smallest hydrophobic chains. {\textcopyright} 2010 Elsevier B.V.
},
	keywords = {amphophile, animal cell, animal experiment, article, Biological membranes, Biomedical applications, cation, Cations, Cell culture, cell membrane transport, cell type, Cellular uptake, controlled study, Cytotoxicity, dendrimer, Dendrimers, DNA, DNA binding, Dyes, Functional polymers, Gene delivery, gene delivery system, gene expression, Gene therapy, Gene transfer, Gene Transfer Techniques, gene vector, Genes, genetic transfection, Genetic Vectors, Humans, Hydrocarbons, hydrophilicity, hydrophobicity, internalization, lipid, Lipids, male, Mesenchymal stem cell, Mesenchymal Stem Cells, nonhuman, nuclease, Nucleic acids, plasmid DNA, Plasmids, Poly(amidoamine) dendrimers, polyamidoamine, Polyamidoamine dendrimers, priority journal, rat, Regenerative Medicine, Stem cells, Transfection, Vectors, Zeta potential},
	isbn = {01683659 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-77953239685\&partnerID=40\&md5=51dd40fc4a666fd362b5eaa2447703dd},
	author = {Santos, J.L. and Oliveira, H. and Pandita, D. and Rodrigues, J. and P{\^e}go, A.P. and Granja, P.L. and Tom{\'a}s, H.}
}
@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},
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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.}
}
