Targeting, Endocytosis, and Lysosomal Delivery of Active Enzymes to Model Human Neurons by ICAM-I-Targeted Nanocarriers

Purpose Delivery of therapeutics to neurons is paramount to treat neurological conditions, including many lysosomal storage disorders. However, key aspects of drug-carrier behavior in neurons are relatively unknown: the occurrence of non-canonical endocytic pathways (present in other cells); whether...

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Authors: Hsu J, Hoenicka J, Muro S
Format: article
Status:Published version
Publication Date:2015
Country:España
Institution:Fundació Sant Joan de Déu
Repository:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p19454
Online Access:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19454
Access Level:Open access
Keyword:CAM-mediated endocytosis
ICAM-I-targeted nanocarriers
Lysosomal transport
neuroblastoma cells
neuronal body vs. neurites
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spelling Targeting, Endocytosis, and Lysosomal Delivery of Active Enzymes to Model Human Neurons by ICAM-I-Targeted NanocarriersHsu JHoenicka JMuro SCAM-mediated endocytosisICAM-I-targeted nanocarriersLysosomal transportneuroblastoma cellsneuronal body vs. neuritesPurpose Delivery of therapeutics to neurons is paramount to treat neurological conditions, including many lysosomal storage disorders. However, key aspects of drug-carrier behavior in neurons are relatively unknown: the occurrence of non-canonical endocytic pathways (present in other cells); whether carriers that traverse the blood-brain barrier are, contrarily, retained within neurons; if neuron-surface receptors are accessible to bulky carriers compared to small ligands; or if there are differences regarding neuronal compartments (neuron body vs. neurites) pertaining said parameters. We have explored these questions using model polymer nanocarriers targeting intercellular adhesion molecule-1 (ICAM-1). Methods Differentiated human neuroblastoma cells were incubated with anti-ICAM-coated polystyrene nanocarriers and analyzed by fluorescence microscopy. Results ICAM-1 expression and nanocarrier binding was enhanced in altered (TNF alpha) vs. control conditions. While small ICAM-1 ligands (anti-ICAM) preferentially accessed the cell body, anti-ICAM nanocarriers bound with faster kinetics to neurites, yet reached similar saturation over time. Anti-ICAM nanocarriers were also endocytosed with faster kinetics and lower saturation levels in neurites. Non-classical cell adhesion molecule (CAM) endocytosis ruled uptake, and neurite-to-cell body transport was inferred. Nanocarriers trafficked to lysosomes, delivering active enzymes (dextranase) with substrate reduction in a lysosomal-storage disease model. Conclusion ICAM-1-targeting holds potential for intracellular delivery of therapeutics to neurons.KLUWER ACADEMIC/PLENUM PUBL2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19454PHARMACEUTICAL RESEARCHISSN: 07248741ISSNe: 1573904Xreponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p194542026-05-27T12:37:41Z
dc.title.none.fl_str_mv Targeting, Endocytosis, and Lysosomal Delivery of Active Enzymes to Model Human Neurons by ICAM-I-Targeted Nanocarriers
title Targeting, Endocytosis, and Lysosomal Delivery of Active Enzymes to Model Human Neurons by ICAM-I-Targeted Nanocarriers
spellingShingle Targeting, Endocytosis, and Lysosomal Delivery of Active Enzymes to Model Human Neurons by ICAM-I-Targeted Nanocarriers
Hsu J
CAM-mediated endocytosis
ICAM-I-targeted nanocarriers
Lysosomal transport
neuroblastoma cells
neuronal body vs. neurites
title_short Targeting, Endocytosis, and Lysosomal Delivery of Active Enzymes to Model Human Neurons by ICAM-I-Targeted Nanocarriers
title_full Targeting, Endocytosis, and Lysosomal Delivery of Active Enzymes to Model Human Neurons by ICAM-I-Targeted Nanocarriers
title_fullStr Targeting, Endocytosis, and Lysosomal Delivery of Active Enzymes to Model Human Neurons by ICAM-I-Targeted Nanocarriers
title_full_unstemmed Targeting, Endocytosis, and Lysosomal Delivery of Active Enzymes to Model Human Neurons by ICAM-I-Targeted Nanocarriers
title_sort Targeting, Endocytosis, and Lysosomal Delivery of Active Enzymes to Model Human Neurons by ICAM-I-Targeted Nanocarriers
dc.creator.none.fl_str_mv Hsu J
Hoenicka J
Muro S
author Hsu J
author_facet Hsu J
Hoenicka J
Muro S
author_role author
author2 Hoenicka J
Muro S
author2_role author
author
dc.subject.none.fl_str_mv CAM-mediated endocytosis
ICAM-I-targeted nanocarriers
Lysosomal transport
neuroblastoma cells
neuronal body vs. neurites
topic CAM-mediated endocytosis
ICAM-I-targeted nanocarriers
Lysosomal transport
neuroblastoma cells
neuronal body vs. neurites
description Purpose Delivery of therapeutics to neurons is paramount to treat neurological conditions, including many lysosomal storage disorders. However, key aspects of drug-carrier behavior in neurons are relatively unknown: the occurrence of non-canonical endocytic pathways (present in other cells); whether carriers that traverse the blood-brain barrier are, contrarily, retained within neurons; if neuron-surface receptors are accessible to bulky carriers compared to small ligands; or if there are differences regarding neuronal compartments (neuron body vs. neurites) pertaining said parameters. We have explored these questions using model polymer nanocarriers targeting intercellular adhesion molecule-1 (ICAM-1). Methods Differentiated human neuroblastoma cells were incubated with anti-ICAM-coated polystyrene nanocarriers and analyzed by fluorescence microscopy. Results ICAM-1 expression and nanocarrier binding was enhanced in altered (TNF alpha) vs. control conditions. While small ICAM-1 ligands (anti-ICAM) preferentially accessed the cell body, anti-ICAM nanocarriers bound with faster kinetics to neurites, yet reached similar saturation over time. Anti-ICAM nanocarriers were also endocytosed with faster kinetics and lower saturation levels in neurites. Non-classical cell adhesion molecule (CAM) endocytosis ruled uptake, and neurite-to-cell body transport was inferred. Nanocarriers trafficked to lysosomes, delivering active enzymes (dextranase) with substrate reduction in a lysosomal-storage disease model. Conclusion ICAM-1-targeting holds potential for intracellular delivery of therapeutics to neurons.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19454
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19454
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv KLUWER ACADEMIC/PLENUM PUBL
publisher.none.fl_str_mv KLUWER ACADEMIC/PLENUM PUBL
dc.source.none.fl_str_mv PHARMACEUTICAL RESEARCH
ISSN: 07248741
ISSNe: 1573904X
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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