In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles

Cátia DF Lopes,1–3,* Hugo Oliveira,1,* Inês Estevão,1 Liliana Raquel Pires,1 Ana Paula Pêgo1,2,4,5 1INEB – Instituto de Engenharia Biomédica, Universidade do Porto (UPorto), Porto, Portugal; 2i3S – Instituto de Inves...

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Autores principales:	Lopes CDF, Oliveira H, Estevão I, Pires LR, Pêgo AP
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	gene therapy non-viral vector neuron-targeted peripheral neurons Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f2a74c8c712f449d9bd518129fdab5f8
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spelling	oai:doaj.org-article:f2a74c8c712f449d9bd518129fdab5f82021-12-02T05:14:21ZIn vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles1178-2013https://doaj.org/article/f2a74c8c712f449d9bd518129fdab5f82016-06-01T00:00:00Zhttps://www.dovepress.com/in-vivo-targeted-gene-delivery-to-peripheral-neurons-mediated-by-neuro-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Cátia DF Lopes,1–3,* Hugo Oliveira,1,* Inês Estevão,1 Liliana Raquel Pires,1 Ana Paula Pêgo1,2,4,5 1INEB – Instituto de Engenharia Biomédica, Universidade do Porto (UPorto), Porto, Portugal; 2i3S – Instituto de Investigação e Inovação em Saúde, NanoBiomaterials for Targeted Therapies Group, UPorto, Porto, Portugal; 3FMUP – Faculdade de Medicina da Universidade do Porto, Porto, Portugal; 4ICBAS – Instituto de Ciências Biomédicas Abel Salazar, UPorto, Porto, Portugal; 5FEUP – Faculdade de Engenharia da Universidade do Porto, Porto, Portugal *These authors contributed equally to this work Abstract: A major challenge in neuronal gene therapy is to achieve safe, efficient, and minimally invasive transgene delivery to neurons. In this study, we report the use of a nonviral neurotropic poly(ethylene imine)-based nanoparticle that is capable of mediating neuron-specific transfection upon a subcutaneous injection. Nanoparticles were targeted to peripheral neurons by using the nontoxic carboxylic fragment of tetanus toxin (HC), which, besides being neurotropic, is capable of being retrogradely transported from neuron terminals to the cell bodies. Nontargeted particles and naked plasmid DNA were used as control. Five days after treatment by subcutaneous injection in the footpad of Wistar rats, it was observed that 56% and 64% of L4 and L5 dorsal root ganglia neurons, respectively, were expressing the reporter protein. The delivery mediated by HC-functionalized nanoparticles spatially limited the transgene expression, in comparison with the controls. Histological examination revealed no significant adverse effects in the use of the proposed delivery system. These findings demonstrate the feasibility and safety of the developed neurotropic nanoparticles for the minimally invasive delivery of genes to the peripheral nervous system, opening new avenues for the application of gene therapy strategies in the treatment of peripheral neuropathies. Keywords: gene therapy, nonviral vector, neuron-targeted, peripheral neuronsLopes CDFOliveira HEstevão IPires LRPêgo APDove Medical Pressarticlegene therapynon-viral vectorneuron-targetedperipheral neuronsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 2675-2683 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	gene therapy non-viral vector neuron-targeted peripheral neurons Medicine (General) R5-920
spellingShingle	gene therapy non-viral vector neuron-targeted peripheral neurons Medicine (General) R5-920 Lopes CDF Oliveira H Estevão I Pires LR Pêgo AP In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles
description	Cátia DF Lopes,1–3,* Hugo Oliveira,1,* Inês Estevão,1 Liliana Raquel Pires,1 Ana Paula Pêgo1,2,4,5 1INEB – Instituto de Engenharia Biomédica, Universidade do Porto (UPorto), Porto, Portugal; 2i3S – Instituto de Investigação e Inovação em Saúde, NanoBiomaterials for Targeted Therapies Group, UPorto, Porto, Portugal; 3FMUP – Faculdade de Medicina da Universidade do Porto, Porto, Portugal; 4ICBAS – Instituto de Ciências Biomédicas Abel Salazar, UPorto, Porto, Portugal; 5FEUP – Faculdade de Engenharia da Universidade do Porto, Porto, Portugal *These authors contributed equally to this work Abstract: A major challenge in neuronal gene therapy is to achieve safe, efficient, and minimally invasive transgene delivery to neurons. In this study, we report the use of a nonviral neurotropic poly(ethylene imine)-based nanoparticle that is capable of mediating neuron-specific transfection upon a subcutaneous injection. Nanoparticles were targeted to peripheral neurons by using the nontoxic carboxylic fragment of tetanus toxin (HC), which, besides being neurotropic, is capable of being retrogradely transported from neuron terminals to the cell bodies. Nontargeted particles and naked plasmid DNA were used as control. Five days after treatment by subcutaneous injection in the footpad of Wistar rats, it was observed that 56% and 64% of L4 and L5 dorsal root ganglia neurons, respectively, were expressing the reporter protein. The delivery mediated by HC-functionalized nanoparticles spatially limited the transgene expression, in comparison with the controls. Histological examination revealed no significant adverse effects in the use of the proposed delivery system. These findings demonstrate the feasibility and safety of the developed neurotropic nanoparticles for the minimally invasive delivery of genes to the peripheral nervous system, opening new avenues for the application of gene therapy strategies in the treatment of peripheral neuropathies. Keywords: gene therapy, nonviral vector, neuron-targeted, peripheral neurons
format	article
author	Lopes CDF Oliveira H Estevão I Pires LR Pêgo AP
author_facet	Lopes CDF Oliveira H Estevão I Pires LR Pêgo AP
author_sort	Lopes CDF
title	In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles
title_short	In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles
title_full	In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles
title_fullStr	In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles
title_full_unstemmed	In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles
title_sort	in vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/f2a74c8c712f449d9bd518129fdab5f8
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In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles

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